Mu-conopeptides

ABSTRACT

The present invention is to μ-conopeptides, derivatives or pharmaceutically acceptable salts thereof. The present invention is further directed to the use of this peptide, derivatives thereof and pharmaceutically acceptable salts thereof for the treatment of disorders associated with voltage-gated sodium channels. Thus, the μ-conopeptides or derivatives are useful as neuromuscular blocking agents, local anesthetic agents, analgesic agents and neuroprotective agents. The μ-conopeptides are also useful for treating neuromuscular disorders. The invention is further directed to nucleic acid sequences encoding the μ-conopeptides and encoding propeptides, as well as the propeptides.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application is a division of U.S. patent applicationSer. No. 09/910,009 filed on 23 Jul. 2001. The present application isalso related to and claims benefit under 35 USC §119(e) to U.S.provisional patent applications Serial No. 60/219,619 filed on 21 Jul.2000, Ser. No. 60/245,157 filed on 3 Nov. 2000, Ser. No. 60/264,319filed on 29 Jan. 2001 and Ser. No. 60/277,270 filed on 21 Mar. 2001.Each of these applications is incorporated herein by reference.

[0002] This invention was made with Government support under Grant No.PO1 GM48677 awarded by the National Institute of General MedicalSciences, National Institutes of Health, Bethesda, Md. The United StatesGovernment has certain rights in the invention.

BACKGROUND OF THE INVENTION

[0003] The present invention is to μ-conopeptides, derivatives orpharmaceutically acceptable salts thereof. The present invention isfurther directed to the use of this peptide, derivatives thereof andpharmaceutically acceptable salts thereof for the treatment of disordersassociated with voltage-gated sodium channels. Thus, the μ-conopeptidesor derivatives are useful as neuromuscular blocking agents, localanesthetic agents, analgesic agents and neuroprotective agents. Theμ-conopeptides are also useful for treating neuromuscular disorders. Theinvention is further directed to nucleic acid sequences encoding theμ-conopeptides and encoding propeptides, as well as the propeptides.

[0004] The publications and other materials used herein to illuminatethe background of the invention, and in particular, cases to provideadditional details respecting the practice, are incorporated byreference, and for convenience are referenced in the following text byauthor and date and are listed alphabetically by author in the appendedbibliography.

[0005] Conus is a genus of predatory marine gastropods (snails) whichenvenomate their prey. Venomous cone snails use a highly developedprojectile apparatus to deliver their cocktail of toxic conotoxins intotheir prey. In fish-eating species such as Conus magus the cone detectsthe presence of the fish using chemosensors in its siphon and when closeenough extends its proboscis and fires a hollow harpoon-like toothcontaining venom into the fish. This immobilizes the fish and enablesthe cone snail to wind it into its mouth via an attached filament. Forgeneral information on Conus and their venom see the web addressgrimwade.biochem.unimelb. edu.au/cone/referenc.html. Prey capture isaccomplished through a sophisticated arsenal of peptides which targetspecific ion channel and receptor subtypes. Each Conus species venomappears to contain a unique set of 50-200 peptides. The composition ofthe venom differs greatly between species and between individual snailswithin each species, each optimally evolved to paralyze its prey. Theactive components of the venom are small peptides toxins, typically10-40 amino acid residues in length and are typically highly constrainedpeptides due to their high density of disulphide bonds.

[0006] The venoms consist of a large number of different peptidecomponents that when separated exhibit a range of biological activities:when injected into mice they elicit a range of physiological responsesfrom shaking to depression. The paralytic components of the venom thathave been the focus of recent investigation are the α-, ω- andμ-conotoxins. All of these conotoxins act by preventing neuronalcommunication, but each targets a different aspect of the process toachieve this. The α-conotoxins target nicotinic ligand gated channels,the μ-conotoxins target the voltage-gated sodium channels and theω-conotoxins target the voltage-gated calcium channels (Olivera et al.,1985; Olivera et al., 1990). For example a linkage has been establishedbetween α-, αA- & ψ-conotoxins and the nicotinic ligand-gated ionchannel; ω-conotoxins and the voltage-gated calcium channel;μ-conotoxins and the voltage-gated sodium channel; δ-conotoxins and thevoltage-gated sodium channel; κ-conotoxins and the voltage-gatedpotassium channel; conantokins and the ligand-gated glutamate (NMDA)channel.

[0007] However, the structure and function of only a small minority ofthese peptides have been determined to date. For peptides where functionhas been determined, three classes of targets have been elucidated:voltage-gated ion channels; ligand-gated ion channels, andG-protein-linked receptors.

[0008] Conus peptides which target voltage-gated ion channels includethose that delay the inactivation of sodium channels, as well asblockers specific for sodium channels, calcium channels and potassiumchannels. Peptides that target ligand-gated ion channels includeantagonists of NMDA and serotonin receptors, as well as competitive andnoncompetitive nicotinic receptor antagonists. Peptides which act onG-protein receptors include neurotensin and vasopressin receptoragonists. The unprecedented pharmaceutical selectivity of conotoxins isat least in part defined by a specific disulfide bond frameworkscombined with hypervariable amino acids within disulfide loops (for areview see McIntosh et al., 1998).

[0009] There are drugs used in the treatment of pain, which are known inthe literature and to the skilled artisan. See, for example, MerckManual, 16th Ed. (1992). However, there is a demand for more activeanalgesic agents with diminished side effects and toxicity and which arenon-addictive. The ideal analgesic would reduce the awareness of pain,produce analgesia over a wide range of pain types, act satisfactorilywhether given orally or parenterally, produce minimal or no sideeffects, be free from tendency to produce tolerance and drug dependence.

[0010] Due to the high potency and exquisite selectivity of theconopeptides, several are in various stages of clinical development fortreatment of human disorders. For example, two Conus peptides are beingdeveloped for the treatment of pain. The most advanced is ω-conotoxinMVIIA (ziconotide), an N-type calcium channel blocker (see Heading, C.,1999; U.S. Pat. No. 5,859,186). ω-Conotoxin MVIIA, isolated from Conusmagus, is approximately 1000 times more potent than morphine, yet doesnot produce the tolerance or addictive properties of opiates.ω-Conotoxin MVIIA has completed Phase III (final stages) of humanclinical trials and has been approved as a therapeutic agent.ω-Conotoxin MVIIA is introduced into human patients by means of animplantable, programmable pump with a catheter threaded into theintrathecal space. Preclinical testing for use in post-surgical pain isbeing carried out on another Conus peptide, contulakin-G, isolated fromConus geographus (Craig et al. 1999). Contulakin-G is a 16 amino acid0-linked glycopeptide whose C-terminus resembles neurotensin. It is anagonist of neurotensin receptors, but appears significantly more potentthan neurotensin in inhibiting pain in in vivo assays.

[0011] In view of a large number of biologically active substances inConus species it is desirable to further characterize them and toidentify peptides capable of treating disorders involving voltage gatedion channels, such as stroke and pain. Surprisingly, and in accordancewith this invention, Applicants have discovered novel conotoxins thatcan be useful for the treatment of disorders involving voltage gated ionchannels and could address a long felt need for a safe and effectivetreatment.

SUMMARY OF THE INVENTION

[0012] The present invention is to μ-conopeptides, derivatives orpharmaceutically acceptable salts thereof. The present invention isfurther directed to the use of this peptide, derivatives thereof andpharmaceutically acceptable salts thereof for the treatment of disordersassociated with voltage-gated sodium channels. Thus, the μ-conopeptidesor derivatives are useful as neuromuscular blocking agents, localanesthetic agents, analgesic agents and neuroprotective agents. Theμ-conopeptides are also useful for treating neuromuscular disorders. Theinvention is further directed to nucleic acid sequences encoding theμ-conopeptides and encoding propeptides, as well as the propeptides.

[0013] More specifically, the present invention is directed toμ-conopeptides, having the amino acid sequences set forth in Tables 1and 2 below.

[0014] The present invention is also directed to derivatives orpharmaceutically acceptable salts of the μ-conopeptides or thederivatives. Examples of derivatives include peptides in which the Argresidues may be substituted by Lys, omithine, homoargine, nor-Lys,N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any syntheticbasic amino acid; the Lys residues may be substituted by Arg, ornithine,homoargine, nor-Lys, or any synthetic basic amino acid; the Tyr residuesmay be substituted with meta-Tyr, ortho-Tyr, nor-Tyr, mono-halo-Tyr,di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any synthetichydroxy containing amino acid; the Ser residues may be substituted withThr or any synthetic hydroxylated amino acid; the Thr residues may besubstituted with Ser or any synthetic hydroxylated amino acid; the Pheresidues may be substituted with any synthetic aromatic amino acid; theTrp residues may be substituted with Trp (D), neo-Trp, halo-Trp (D or L)or any aromatic synthetic amino acid; and the Asn, Ser, Thr or Hypresidues may be glycosylated. The halogen may be iodo, chloro, fluoro orbromo; preferably iodo for halogen substituted-Tyr and bromo forhalogen-substituted Trp. The Tyr residues may also be substituted withthe 3-hydroxyl or 2-hydroxyl isomers (meta-Tyr or ortho-Tyr,respectively) and corresponding O-sulpho- and O-phospho-derivatives. Theacidic amino acid residues may be substituted with any synthetic acidicamino acid, e.g., tetrazolyl derivatives of Gly and Ala. The aliphaticamino acids may be substituted by synthetic derivatives bearingnon-natural aliphatic branched or linear side chains C_(n)H_(2n+2) up toand including n=8. The Met residues may be substituted by norleucine(Nle). The Cys residues may be in D or L configuration and mayoptionally be substituted with homocysteine (D or L).

[0015] Examples of synthetic aromatic amino acid include, but are notlirnited to, nitro-Phe, 4-substituted-Phe wherein the substituent isC₁-C₃ alkyl, carboxyl, hyrdroxymethyl, sulphomethyl, halo, phenyl, —CHO,—CN, —SO₃H and —NHAc. Examples of synthetic hydroxy containing aminoacid, include, but are not limited to, such as 4-hydroxymethyl-Phe,4-hydroxyphenyl-Gly, 2,6-dimethyl-Tyr and 5-amino-Tyr. Examples ofsynthetic basic amino acids include, but are not limited to,N-1-(2-pyrazolinyl)-Arg, 2-(4-piperinyl)-Gly, 2-(4-piperinyl)-Ala,2-[3-(2S)pyrrolininyl)-Gly and 2-[3-(2S)pyrrolininyl)-Ala. These andother synthetic basic amino acids, synthetic hydroxy containing aminoacids or synthetic aromatic amino acids are described in Building BlockIndex, Version 3.0 (1999 Catalog, pages 4-47 for hydroxy containingamino acids and aromatic amino acids and pages 66-87 for basic aminoacids; see also web address amino-acids. com), incorporated herein byreference, by and available from RSP Amino Acid Analogues, Inc.,Worcester, Mass. Examples of synthetic acid amino acids include thosederivatives bearing acidic functionality, including carboxyl, phosphate,sulfonate and synthetic tetrazolyl derivatives such as described byOrnstein et al. (1993) and in U.S. Pat. No. 5,331,001, each incorporatedherein by reference.

[0016] Optionally, in the μ-conopeptides of the present invention, theAsn residues may be modified to contain an N-glycan and the Ser, Thr andHyp residues may be modified to contain an O-glycan (e.g., g-N, g-S, g-Tand g-Hyp). In accordance with the present invention, a glycan shallmean any N-, S- or O-linked mono-, di-, tri-, poly- or oligosaccharidethat can be attached to any hydroxy, amino or thiol group of natural ormodified amino acids by synthetic or enzymatic methodologies known inthe art. The monosaccharides making up the glycan can include D-allose,D-altrose, D-glucose, D-mannose, D-gulose, D-idose, D-galactose,D-talose, D-galactosamine, D-glucosamine, D-N-acetyl-glucosamine(GlcNAc), D-N-acetyl-galactosamine (GalNAc), D-fucose or D-arabinose.These saccharides may be structurally modified, e.g., with one or moreO-sulfate, O-phosphate, O-acetyl or acidic groups, such as sialic acid,including combinations thereof. The gylcan may also include similarpolyhydroxy groups, such as D-penicillamine 2,5 and halogenatedderivatives thereof or polypropylene glycol derivatives. The glycosidiclinkage is beta and 1-4 or 1-3, preferably 1-3. The linkage between theglycan and the amino acid may be alpha or beta, preferably alpha and is1-.

[0017] Core O-glycans have been described by Van de Steen et al. (1998),incorporated herein by reference. Mucin type O-linked oligosaccharidesare attached to Ser or Thr (or other hydroxylated residues of thepresent peptides) by a GalNAc residue. The monosaccharide buildingblocks and the linkage attached to this first GalNAc residue define the“core glycans,” of which eight have been identified. The type ofglycosidic linkage (orientation and connectivities) are defined for eachcore glycan. Suitable glycans and glycan analogs are described furtherin U.S. Ser. No. 09/420,797 filed 19 Oct. 1999 (now U.S. Pat. No.6,369,193) and in PCT Application No. PCT/US99/24380 filed 19 Oct. 1999(PCT Published Application No. WO 00/23092), each incorporated herein byreference. A preferred glycan is Gal(β1→3)GalNAc(α1→).

[0018] Optionally, in the μ-conopeptides described above, pairs of Cysresidues may be replaced pairwise with isoteric lactam orester-thioether replacements, such as Ser/(Glu or Asp), Lys/(Glu orAsp), Cys/(Glu or Asp) or Cys/Ala combinations. Sequential coupling byknown methods (Barnay et al., 2000; Hruby et al., 1994; Bitan et al.,1997) allows replacement of native Cys bridges with lactam bridges.Thioether analogs may be readily synthesized using halo-Ala residuescommercially available from RSP Amino Acid Analogues.

[0019] The present invention is further directed to derivatives of theabove peptides and peptide derivatives which are acylic permutations inwhich the cyclic permutants retain the native bridging pattern of nativetoxin. See, for example, Craik et al. (2001).

[0020] The present invention is further directed to a method of treatingdisorders associated with voltage gated ion channel disorders in asubject comprising administering to the subject an effective amount ofthe pharmaceutical composition comprising a therapeutically effectiveamount of a μ-conopeptide described herein or a pharmaceuticallyacceptable salt or solvate thereof. The present invention is alsodirected to a pharmaceutical composition comprising a therapeuticallyeffective amount of a μ-conopeptide described herein or apharmaceutically acceptable salt or solvate thereof and apharmaceutically acceptable carrier.

[0021] More specifically, the present invention is further directed touses of these peptides or nucleic acids as described herein asneuromuscular blocking agents, local anesthetic agents, analgesic agentsand neuroprotective agents. The μ-conopeptides are also useful fortreating neuromuscular disorders.

[0022] The present invention is directed to the use of μ-conopeptides asa local anesthetic for treating pain. The μ-conopeptides have longlasting anesthetic activity and are particularly useful for spinalanesthesia, either administered acutely for post-operative pain or viaan intrathecal pump for severe chronic pain situations. Theμ-conopeptides are also useful as analgesics in chronic and neuropathicpain states, such as trigeminal neuralgia, diabetic neuropathy,post-herpetic neuralgia, neuroma pain and phantom limb pain. Theμ-conopeptides are also useful for treating burn pain and as ocularanesthetics.

[0023] The present invention is directed to the use of μ-conopeptides asneuroprotectants. The μ-conopeptides are useful for the treatment andalleviation of epilepsy and as a general anticonvulsant agent. Theμ-conopeptides are also useful for treating neurodegenerative diseases,such as Amyotrophic Lateral Sclerosis (ALS). The μ-conopeptides arefurther useful as cerebroprotectants, such as for reducing neurotoxicinjury associated with conditions of hypoxia, anoxia or ischemia whichtypically follows stroke, cerebrovascular accident, brain or spinal cordtrauma, myocardial infarct, physical trauma, drowning, suffocation,perinatal asphyxia, or hypoglycemic events.

[0024] The present invention is directed to the use of μ-conopeptides asneuromuscular blockers and for treating neuromuscular disorders. Assuch, the μ-conopeptides are useful for providing relaxation of muscle,for treating benign essential blepharospasm and other forms of focaldystonia and for anti-wrinkle use.

[0025] More specifically, the present invention is also directed tonucleic acids which encode μ-conopeptides of the present invention orwhich encodes precursor peptides for these μ-conopeptides, as well asthe precursor peptide. The nucleic acid sequences encoding the precursorpeptides of other μ-conopeptides of the present invention are set forthin Table 1. Table 1 also sets forth the amino acid sequences of theseprecursor peptides.

[0026] The present invention is further directed to the use ofselectively radioiodinated or radiotritiated μ-conopeptides forcharacterizing pore occlusion sites on different sodium channel subtypesor for use in screening assays.

[0027] The present invention is also directed to the use ofμ-conopeptides for screening small molecule libraries to identify smallmolecules that are selective blocking agents at specific sodium channelsubtypes expressed in mammalian systems. In one embodiment, the blockingactivity of a small molecule at a particular sodium channel subtype iscompared to the blocking activity of a μ-conopeptide at the same sodiumchannel subtype. In a second embodiment, the ability of a small moleculeto displace a μ-conopeptide from a sodium channel subtype is determined.In a third emdiment, the binding affinity of a small molecule for asodium channel subtype is compared to the binding affinity of aμ-conopeptide for the same sodium channel subtype.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0028] The present invention is to μ-conopeptides, derivatives orpharmaceutically acceptable salts thereof. The present invention isfurther directed to the use of this peptide, derivatives thereof andpharmaceutically acceptable salts thereof for the treatment of disordersassociated with voltage-gated sodium channels. Thus, the μ-conopeptidesor derivatives are useful as neuromuscular blocking agents, localanesthetic agents, analgesic agents and neuroprotective agents. Theμ-conopeptides are also useful for treating neuromuscular disorders. Theinvention is further directed to nucleic acid sequences encoding theμ-conopeptides and encoding propeptides, as well as the propeptides.

[0029] The present invention, in another aspect, relates to apharmaceutical composition comprising an effective amount of anμ-conopeptides, a mutein thereof, an analog thereof, an active fragmentthereof or pharmaceutically acceptable salts or solvates. Such apharmaceutical composition has the capability of acting at voltage gatedion channels, and are thus useful for treating a disorder or disease ofa living animal body, including a human, which disorder or disease isresponsive to the partial or complete blockade of voltage gated ionchannels of the central nervous system comprising the step ofadministering to such a living animal body, including a human, in needthereof a therapeutically effective amount of a pharmaceuticalcomposition of the present invention.

[0030] The present invention is directed to the use of μ-conopeptides asneuromuscular blockers and for treating neuromuscular disorders. Assuch, the μ-conopeptides are useful for providing relaxation of muscle,for treating benign essential blepharospasm and other forms of focaldystonia and for anti-wrinkle use. Thus, in one aspect, theμ-conopeptides are useful as neurmuscular blocking agents in conjunctionwith surgery or for intubation of the trachea by conventional parenteraladministration e.g., intramuscular or intravenous administration insolution. In a second aspect, the μ-conopeptides are useful as agentsfor treating neuromuscular disorders such as myofacial pain syndrome,chronic muscle spasm, dystonias and spasticity.

[0031] The primary factor detrimental to neurons in neurologicaldisorders associated with deficient oxygen supply or mitochondrialdysfunction is insufficient ATP production relative to theirrequirement. As a large part of the energy consumed by brain cells isused for maintenance of the Na⁺ gradient across the cellular membrane,reduction of energy demand by down-modulation of voltage-gatedNa(+)-channels is one strategy for neuroprotection. In addition,preservation of the inward Na⁺ gradient may be beneficial because it isan essential driving force for vital ion exchanges and transportmechanisms such as Ca²⁺ homeostasis and neurotransmitter uptake. Thus,the μ-conopeptides of the present invention are useful asneuroprotectants.

[0032] Thus, the pharmaceutical compositions of the present inventionare useful as neuroprotectants, especially cerebroprotectants,neuromuscular blockers, analgesics (both as a local anesthetic and forgeneral analgesia use) or adjuvants to general anesthetics. A“neurological disorder or disease” is a disorder or disease of thenervous system including, but not limited to, global and focal ischemicand hemorrhagic stroke, head trauma, spinal cord injury, hypoxia-inducednerve cell damage as in cardiac arrest or neonatal distress or epilepsy.In addition, a “neurological disorder or disease” is a disease state andcondition in which a neuroprotectant, anticonvulsant, analgesic and/oras an adjunct in general anesthesia may be indicated, useful,recommended or prescribed.

[0033] More specifically, the present invention is directed to the useof these compounds for reducing neurotoxic injury associated withconditions of hypoxia, anoxia or ischemia which typically followsstroke, cerebrovascular accident, brain or spinal cord trauma,myocardial infarct, physical trauma, drowning, suffocation, perinatalasphyxia, or hypoglycemic events. The present invention is furtherdirected to the use of these compounds for treating pain, includingacute and chronic pain, such migraine, nociceptive and neuropathic pain.

[0034] A “neuroprotectant” is a compound capable of preventing theneuronal death associated with a neurological disorder or disease. An“analgesic” is a compound capable of relieving pain by alteringperception of nociceptive stimuli without producing anesthesia or lossof consciousness. A “muscle relaxant” is a compound that reducesmuscular tension. An “adjunct in general anesthesia” is a compounduseful in conjunction with anesthetic agents in producing the loss ofability to perceive pain associated with the loss of consciousness.

[0035] The invention relates as well to methods useful for treatment ofneurological disorders and diseases, including, but not limited to,global and focal ischemic and hemorrhagic stroke, head trauma, spinalcord injury, hypoxia-induced nerve cell damage such as in cardiac arrestor neonatal distress, epilepsy or other convulsive disorders withoutundesirable side effects.

[0036] Thus, in one embodiment, the invention provides a method ofreducing/alleviating/decreasing the perception of pain by a subject orfor inducing analgesia in a subject comprising administering to thesubject an effective amount of the pharmaceutical composition comprisinga therapeutically effective amount of a μ-conopeptide described hereinor a pharmaceutically acceptable salt or solvate thereof. The pain maybe acute, persistent, inflammatory or neuropathic pain. Theμ-conopeptides are useful as an analgesia for chronic and neuropathicpain states, such as trigeminal neuralgia, diabetic neuropathy,post-herpetic neuralgia, neuroma pain, phantom limb pain. These peptidesare also useful for treating bum pain and as ocular anesthetics.

[0037] In a second embodiment, the invention provides a method ofreducing/alleviating/decreasing the perception of pain by a subject orfor inducing analgesia, particularly local analgesia, in a subjectcomprising administering to the subject an effective amount of thepharmaceutical composition comprising a therapeutically effective amountof a μ-conopeptide described herein or a pharmaceutically acceptablesalt or solvate thereof. These peptides are also useful for treating bumpain and as ocular anesthetics.

[0038] In a third embodiment, the invention provides a method oftreating stroke, head or spinal cord trauma or injury, anoxia,hypoxia-induced nerve cell damage, ischemia, migraine, psychosis,anxiety, schizophrenia, inflammation, movement disorder, epilepsy, anyother convulsive disorder or in the prevention of the degenerativechanges connected with the same in a subject comprising administering tothe subject an effective amount of the pharmaceutical compositioncomprising a therapeutically effective amount of a μ-conopeptidedescribed herein or a pharmaceutically acceptable salt or solvatethereof.

[0039] In a fourth embodiment, the invention provides a method forproviding a neuromuscular block or for treating neuromuscular disorders,such as methods for providing relaxation of muscle, for treating benignessential blepharospasm and other forms of focal dystonia and foranti-wrinkle use. Thus, in one aspect, the μ-conopeptides are useful asneurmuscular blocking agents in conjunction with surgery or forintubation of the trachea by conventional parenteral administratione.g., intramuscular or intravenous administration in solution. In asecond aspect, the μ-conopeptides are useful as agents for treatingneuromuscular disorders such as myofacial pain syndrome, chronic musclespasm, dystonias and spasticity.

[0040] The present invention is also directed to the use ofμ-conopeptides for screening small molecule libraries to identify smallmolecules that are selective blocking agents at specific sodium channelsubtypes expressed in mammalian systems. In one embodiment, the blockingactivity of a small molecule at a particular sodium channel subtype iscompared to the blocking activity of a μ-conopeptide at the same sodiumchannel subtype. In a second embodiment, the ability of a small moleculeto displace a μ-conopeptide from a sodium charmel subtype is determined.In a third emdiment, the binding affinity of a small molecule for asodium channel subtype is compared to the binding affinity of aμ-conopeptide for the same sodium channel subtype.

[0041] The μ-conopeptides described herein are sufficiently small to bechemically synthesized. General chemical syntheses for preparing theforegoing ω-conotoxin peptides are described hereinafter. Various onesof the μ-conopeptides can also be obtained by isolation and purificationfrom specific Conus species using the technique described in U.S. Pat.No. 4,447,356 (Olivera et al., 1984); U.S. Pat. Nos. 5,514,774;5,719,264; and 5,591,821, as well as in PCT published application WO98/03189, the disclosures of which are incorporated herein by reference.

[0042] Although the μ-conopeptides of the present invention can beobtained by purification from cone snails, because the amounts ofμ-conopeptides obtainable from individual snails are very small, thedesired substantially pure μ-conopeptides are best practically obtainedin commercially valuable amounts by chemical synthesis using solid-phasestrategy. For example, the yield from a single cone snail may be about10 micrograms or less of μ-conopeptides peptide. By “substantially pure”is meant that the peptide is present in the substantial absence of otherbiological molecules of the same type; it is preferably present in anamount of at least about 85% purity and preferably at least about 95%purity. Chemical synthesis of biologically active μ-conopeptidespeptides depends of course upon correct determination of the amino acidsequence.

[0043] The μ-conopeptides can also be produced by recombinant DNAtechniques well known in the art. Such techniques are described bySambrook et al. (1989). A gene of interest (i.e., a gene that encodes asuitable μ-conopeptides) can be inserted into a cloning site of asuitable expression vector by using standard techniques. Thesetechniques are well known to those skilled in the art. The expressionvector containing the gene of interest may then be used to transfect thedesired cell line. Standard transfection techniques such as calciumphosphate co-precipitation, DEAE-dextran transfection or electroporationmay be utilized. A wide variety of host/expression vector combinationsmay be used to express a gene encoding a conotoxin peptide of interest.Such combinations are well known to a skilled artisan. The peptidesproduced in this manner are isolated, reduced if necessary, and oxidizedto form the correct disulfide bonds.

[0044] One method of forming disulfide bonds in the μ-conopeptides ofthe present invention is the air oxidation of the linear peptides forprolonged periods under cold room temperatures or at room temperature.This procedure results in the creation of a substantial amount of thebioactive, disulfide-linked peptides. The oxidized peptides arefractionated using reverse-phase high performance liquid chromatography(HPLC) or the like, to separate peptides having different linkedconfigurations. Thereafter, either by comparing these fractions with theelution of the native material or by using a simple assay, theparticular fraction having the correct linkage for maximum biologicalpotency is easily determined. However, because of the dilution resultingfrom the presence of other fractions of less biopotency, a somewhathigher dosage may be required.

[0045] The peptides are synthesized by a suitable method, such as byexclusively solid-phase techniques, by partial solid-phase techniques,by fragment condensation or by classical solution couplings.

[0046] In conventional solution phase peptide synthesis, the peptidechain can be prepared by a series of coupling reactions in whichconstituent amino acids are added to the growing peptide chain in thedesired sequence. Use of various coupling reagents, e.g.,dicyclohexylcarbodiimide or diisopropylcarbonyldimidazole, variousactive esters, e.g., esters of N-hydroxyphthalimide orN-hydroxy-succinimide, and the various cleavage reagents, to carry outreaction in solution, with subsequent isolation and purification ofintermediates, is well known classical peptide methodology. Classicalsolution synthesis is described in detail in the treatise, “Methoden derOrganischen Chemie (Houben-Weyl): Synthese von Peptiden,” (1974).Techniques of exclusively solid-phase synthesis are set forth in thetextbook, “Solid-Phase Peptide Synthesis,” (Stewart and Young, 1969),and are exemplified by the disclosure of U.S. Pat. No. 4,105,603 (Valeet al., 1978). The fragment condensation method of synthesis isexemplified in U.S. Pat. No. 3,972,859 (1976). Other available synthesesare exemplified by U.S. Pat. No. 3,842,067 (1974) and U.S. Pat. No.3,862,925 (1975). The synthesis of peptides containing γ-carboxyglutamicacid residues is exemplified by Rivier et al. (1987), Nishiuchi et al.(1993) and Zhou et al. (1996).

[0047] Common to such chemical syntheses is the protection of the labileside chain groups of the various amino acid moieties with suitableprotecting groups which will prevent a chemical reaction from occurringat that site until the group is ultimately removed. Usually also commonis the protection of an α-amino group on an amino acid or a fragmentwhile that entity reacts at the carboxyl group, followed by theselective removal of the α-amino protecting group to allow subsequentreaction to take place at that location. Accordingly, it is common that,as a step in such a synthesis, an intermediate compound is producedwhich includes each of the amino acid residues located in its desiredsequence in the peptide chain with appropriate side-chain protectinggroups linked to various ones of the residues having labile side chains.

[0048] As far as the selection of a side chain amino protecting group isconcerned, generally one is chosen which is not removed duringdeprotection of the α-amino groups during the synthesis. However, forsome amino acids, e.g., His, protection is not generally necessary. Inselecting a particular side chain protecting group to be used in thesynthesis of the peptides, the following general rules are followed: (a)the protecting group preferably retains its protecting properties and isnot split off under coupling conditions, (b) the protecting group shouldbe stable under the reaction conditions selected for removing theα-amino protecting group at each step of the synthesis, and (c) the sidechain protecting group must be removable, upon the completion of thesynthesis containing the desired amino acid sequence, under reactionconditions that will not undesirably alter the peptide chain.

[0049] It should be possible to prepare many, or even all, of thesepeptides using recombinant DNA technology. However, when peptides arenot so prepared, they are preferably prepared using the Merrifieldsolid-phase synthesis, although other equivalent chemical synthesesknown in the art can also be used as previously mentioned. Solid-phasesynthesis is commenced from the C-terminus of the peptide by coupling aprotected α-amino acid to a suitable resin. Such a starting material canbe prepared by attaching an α-amino-protected amino acid by an esterlinkage to a chloromethylated resin or a hydroxymethyl resin, or by anamide bond to a benzhydrylamine (BHA) resin or paramethylbenzhydrylamine(MBHA) resin. Preparation of the hydroxymethyl resin is described byBodansky et al. (1966). Chloromethylated resins are commerciallyavailable from Bio Rad Laboratories (Richmond, Calif.) and from Lab.Systems, Inc. The preparation of such a resin is described by Stewartand Young (1969). BHA and MBHA resin supports are commerciallyavailable, and are generally used when the desired polypeptide beingsynthesized has an unsubstituted amide at the C-terminus. Thus, solidresin supports may be any of those known in the art, such as one havingthe formulae —O—CH₂-resin support, —NH BHA resin support, or —NH—MBHAresin support. When the unsubstituted amide is desired, use of a BHA orMBHA resin is preferred, because cleavage directly gives the amide. Incase the N-methyl amide is desired, it can be generated from an N-methylBHA resin. Should other substituted amides be desired, the teaching ofU.S. Pat. No. 4,569,967 (Kornreich et al., 1986) can be used, or shouldstill other groups than the free acid be desired at the C-terminus, itmay be preferable to synthesize the peptide using classical methods asset forth in the Houben-Weyl text (1974).

[0050] The C-terminal amino acid, protected by Boc or Fmoc and by aside-chain protecting group, if appropriate, can be first coupled to achloromethylated resin according to the procedure set forth in K. Horikiet al. (1978), using KF in DMF at about 60° C. for 24 hours withstirring, when a peptide having free acid at the C-terminus is to besynthesized. Following the coupling of the BOC-protected amino acid tothe resin support, the α-amino protecting group is removed, as by usingtrifluoroacetic acid (TFA) in methylene chloride or TFA alone. Thedeprotection is carried out at a temperature between about 0° C. androom temperature. Other standard cleaving reagents, such as HCl indioxane, and conditions for removal of specific α-amino protectinggroups may be used as described in Schroder & Lubke (1965).

[0051] After removal of the α-amino-protecting group, the remainingα-amino- and side chain-protected amino acids are coupled step-wise inthe desired order to obtain the intermediate compound definedhereinbefore, or as an alternative to adding each amino acid separatelyin the synthesis, some of them may be coupled to one another prior toaddition to the solid phase reactor. Selection of an appropriatecoupling reagent is within the skill of the art. Particularly suitableas a coupling reagent is N,N′-dicyclohexylcarbodiimide (DCC, DIC, HBTU,HATU, TBTU in the presence of HoBt or HoAt).

[0052] The activating reagents used in the solid phase synthesis of thepeptides are well known in the peptide art. Examples of suitableactivating reagents are carbodiimides, such asN,N′-diisopropylcarbodiimide andN-ethyl-N′-(3-dimethylaminopropyl)carbodiimide. Other activatingreagents and their use in peptide coupling are described by Schroder &Lubke (1965) and Kapoor (1970).

[0053] Each protected amino acid or amino acid sequence is introducedinto the solid-phase reactor in about a twofold or more excess, and thecoupling may be carried out in a medium of dimethylformamide(DMF):CH₂Cl₂ (1:1) or in DMF or CH₂Cl₂ alone. In cases whereintermediate coupling occurs, the coupling procedure is repeated beforeremoval of the α-amino protecting group prior to the coupling of thenext amino acid. The success of the coupling reaction at each stage ofthe synthesis, if performed manually, is preferably monitored by theninhydrin reaction, as described by Kaiser et al. (1970). Couplingreactions can be performed automatically, as on a Beckman 990 automaticsynthesizer, using a program such as that reported in Rivier et al.(1978).

[0054] After the desired amino acid sequence has been completed, theintermediate peptide can be removed from the resin support by treatmentwith a reagent, such as liquid hydrogen fluoride or TFA (if using Fmocchemistry), which not only cleaves the peptide from the resin but alsocleaves all remaining side chain protecting groups and also the -aminoprotecting group at the N-terminus if it was not previously removed toobtain the peptide in the form of the free acid. If Met is present inthe sequence, the Boc protecting group is preferably first removed usingtrifluoroacetic acid (TFA)/ethanedithiol prior to cleaving the peptidefrom the resin with HF to eliminate potential S-alkylation. When usinghydrogen fluoride or TFA for cleaving, one or more scavengers such asanisole, cresol, dimethyl sulfide and methylethyl sulfide are includedin the reaction vessel.

[0055] Cyclization of the linear peptide is preferably affected, asopposed to cyclizing the peptide while a part of the peptido-resin, tocreate bonds between Cys residues. To effect such a disulfide cyclizinglinkage, fully protected peptide can be cleaved from a hydroxymethylatedresin or a chloromethylated resin support by ammonolysis, as is wellknown in the art, to yield the fully protected amide intermediate, whichis thereafter suitably cyclized and deprotected. Alternatively,deprotection, as well as cleavage of the peptide from the above resinsor a benzhydrylamine (BHA) resin or a methylbenzhydrylamine (MBHA), cantake place at 0° C. with hydrofluoric acid (HF) or TFA, followed byoxidation as described above.

[0056] The peptides are also synthesized using an automatic synthesizer.Amino acids are sequentially coupled to an MBHA Rink resin (typically100 mg of resin) beginning at the C-terminus using an Advanced Chemtech357 Automatic Peptide Synthesizer. Couplings are carried out using1,3-diisopropylcarbodimide in N-methylpyrrolidinone (NMP) or by2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate(HBTU) and diethylisopro-pylethylamine (DIEA). The FMOC protecting groupis removed by treatment with a 20% solution of piperidine indimethylformamide(DMF). Resins are subsequently washed with DMF (twice),followed by methanol and NMP.

[0057] Muteins, analogs or active fragments, of the foregoing conotoxinpeptides are also contemplated here. See, e.g., Hammerland et al.(1992). Derivative muteins, analogs or active fragments of the conotoxinpeptides may be synthesized according to known techniques, includingconservative amino acid substitutions, such as outlined in U.S. Pat. No.5,545,723 (see particularly col. 2, line 50—col. 3, line 8); U.S. Pat.No. 5,534,615 (see particularly col. 19, line 45—col 22, line 33); andU.S. Pat. No. 5,364,769 (see particularly col. 4, line 55—col. 7, line26), each herein incorporated by reference.

[0058] The μ-conopeptides of the present invention are also useful toreduce neurotoxic injury associated with conditions of hypoxia, anoxiaor ischemia which typically follows stroke, cerebrovascular accident,brain or spinal chord trauma, myocardial infarct, physical trauma,drownings, suffocation, perinatal asphyxia, or hypoglycemic events. Toreduce neurotoxic injury, an ω-conopeptide should be administered in atherapeutically effective amount to the patient within 24 hours of theonset of the hypoxic, anoxic or ischemic condition in order for theμ-conopeptide to effectively minimize the CNS damage which the patientwill experience.

[0059] The μ-conopeptides of the present invention are further useful incontrolling pain, e.g., as analgesic agents, and the treatment ofmigraine, acute pain or persistent pain. They can be usedprophylactically or to relieve the symptoms associated with a migraineepisode, or to treat acute or persistent pain. For these uses, anμ-conopeptide is administered in a therapeutically effective amount toovercome or to ease the pain.

[0060] The μ-conopeptides of the present invention are also useful asneuromuscular blockers and for treating neuromuscular disorders. Theycan be used for providing relaxation of muscle, for treating benignessential blepharospasm and other forms of focal dystonia and foranti-wrinkle use. Thus, in one aspect, the μ-conopeptides are used asneurmuscular blocking agents in conjunction with surgery or forintubation of the trachea by conventional parenteral administratione.g., intramuscular or intravenous administration in solution. In asecond aspect, the μ-conopeptides are used as agents for treatingneuromuscular disorders such as myofacial pain syndrome, chronic musclespasm, dystonias and spasticity. For these uses, a μ-conopeptide isadministered in a therapeutically effective amount to relax muscle orprovide a neuromuscular block.

[0061] Pharmaceutical compositions containing a compound of the presentinvention as the active ingredient can be prepared according toconventional pharmaceutical compounding techniques. See, for example,Remington's Pharmaceutical Sciences, 18th Ed. (1990, Mack PublishingCo., Easton, Pa.). Typically, an antagonistic amount of activeingredient will be admixed with a pharmaceutically acceptable carrier.The carrier may take a wide variety of forms depending on the form ofpreparation desired for administration, e.g., intravenous, oral,parenteral or intrathecally. For examples of delivery methods see U.S.Pat. No. 5,844,077, incorporated herein by reference.

[0062] “Pharmaceutical composition” means physically discrete coherentportions suitable for medical administration. “Pharmaceuticalcomposition in dosage unit form” means physically discrete coherentunits suitable for medical administration, each containing a daily doseor a multiple (up to four times) or a sub-multiple (down to a fortieth)of a daily dose of the active compound in association with a carrierand/or enclosed within an envelope. Whether the composition contains adaily dose, or for example, a half, a third or a quarter of a dailydose, will depend on whether the pharmaceutical composition is to beadministered once or, for example, twice, three times or four times aday, respectively.

[0063] The term “salt”, as used herein, denotes acidic and/or basicsalts, formed with inorganic or organic acids and/or bases, preferablybasic salts. While pharmaceutically acceptable salts are preferred,particularly when employing the compounds of the invention asmedicaments, other salts find utility, for example, in processing thesecompounds, or where non-medicament-type uses are contemplated. Salts ofthese compounds may be prepared by art-recognized techniques.

[0064] Examples of such pharmaceutically acceptable salts include, butare not limited to, inorganic and organic addition salts, such ashydrochloride, sulphates, nitrates or phosphates and acetates,trifluoroacetates, propionates, succinates, benzoates, citrates,tartrates, fumarates, maleates, methane-sulfonates, isothionates,theophylline acetates, salicylates, respectively, or the like. Loweralkyl quaternary ammonium salts and the like are suitable, as well.

[0065] As used herein, the term “pharmaceutically acceptable” carriermeans a non-toxic, inert solid, semi-solid liquid filler, diluent,encapsulating material, formulation auxiliary of any type, or simply asterile aqueous medium, such as saline. Some examples of the materialsthat can serve as pharmaceutically acceptable carriers are sugars, suchas lactose, glucose and sucrose, starches such as corn starch and potatostarch, cellulose and its derivatives such as sodium carboxymethylcellulose, ethyl cellulose and cellulose acetate; powdered tragacanth;malt, gelatin, talc; excipients such as cocoa butter and suppositorywaxes; oils such as peanut oil, cottonseed oil, safflower oil, sesameoil, olive oil, corn oil and soybean oil; glycols, such as propyleneglycol, polyols such as glycerin, sorbitol, mannitol and polyethyleneglycol; esters such as ethyl oleate and ethyl laurate, agar; bufferingagents such as magnesium hydroxide and aluminum hydroxide; alginic acid;pyrogen-free water; isotonic saline, Ringer's solution; ethyl alcoholand phosphate buffer solutions, as well as other non-toxic compatiblesubstances used in pharmaceutical formulations.

[0066] Wetting agents, emulsifiers and lubricants such as sodium laurylsulfate and magnesium stearate, as well as coloring agents, releasingagents, coating agents, sweetening, flavoring and perfuming agents,preservatives and antioxidants can also be present in the composition,according to the judgment of the formulator. Examples ofpharmaceutically acceptable antioxidants include, but are not limitedto, water soluble antioxidants such as ascorbic acid, cysteinehydrochloride, sodium bisulfite, sodium metabisulfite, sodium sulfite,and the like; oil soluble antioxidants, such as ascorbyl palmitate,butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT),lecithin, propyl gallate, aloha-tocopherol and the like; and the metalchelating agents such as citric acid, ethylenediamine tetraacetic acid(EDTA), sorbitol, tartaric acid, phosphoric acid and the like.

[0067] For oral administration, the compounds can be formulated intosolid or liquid preparations such as capsules, pills, tablets, lozenges,melts, powders, suspensions or emulsions. In preparing the compositionsin oral dosage form, any of the usual pharmaceutical media may beemployed, such as, for example, water, glycols, oils, alcohols,flavoring agents, preservatives, coloring agents, suspending agents, andthe like in the case of oral liquid preparations (such as, for example,suspensions, elixirs and solutions); or carriers such as starches,sugars, diluents, granulating agents, lubricants, binders,disintegrating agents and the like in the case of oral solidpreparations (such as, for example, powders, capsules and tablets).Because of their ease in administration, tablets and capsules representthe most advantageous oral dosage unit form, in which case solidpharmaceutical carriers are obviously employed. If desired, tablets maybe sugar-coated or enteric-coated by standard techniques. The activeagent can be encapsulated to make it stable to passage through thegastrointestinal tract while at the same time allowing for passageacross the blood brain barrier. See for example, WO 96/11698.

[0068] For parenteral administration, the compound may be dissolved in apharmaceutical carrier and administered as either a solution or asuspension. Illustrative of suitable carriers are water, saline,dextrose solutions, fructose solutions, ethanol, or oils of animal,vegetative or synthetic origin. The carrier may also contain otheringredients, for example, preservatives, suspending agents, solubilizingagents, buffers and the like. When the compounds are being administeredintrathecally, they may also be dissolved in cerebrospinal fluid.

[0069] A variety of administration routes are available. The particularmode selected will depend of course, upon the particular drug selected,the severity of the disease state being treated and the dosage requiredfor therapeutic efficacy. The methods of this invention, generallyspeaking, may be practiced using any mode of administration that ismedically acceptable, meaning any mode that produces effective levels ofthe active compounds without causing clinically unacceptable adverseeffects. Such modes of administration include oral, rectal, sublingual,topical, nasal, transdermal or parenteral routes. The term “parenteral”includes subcutaneous, intravenous, epidural, irrigation, intramuscular,release pumps, or infusion.

[0070] For example, administration of the active agent according to thisinvention may be achieved using any suitable delivery means, including:

[0071] (a) pump (see, e.g., Luer & Hatton (1993), Zimm et al. (1984) andEttinger et al. (1978));

[0072] (b), microencapsulation (see, e.g., U.S. Pat. Nos. 4,352,883;4,353,888; and 5,084,350);

[0073] (c) continuous release polymer implants (see, e.g., U.S. Pat. No.4,883,666);

[0074] (d) macroencapsulation (see, e.g., U.S. Pat. Nos. 5,284,761,5,158,881, 4,976,859 and 4,968,733 and published PCT patent applicationsWO92/19195, WO 95/05452);

[0075] (e) naked or unencapsulated cell grafts to the CNS (see, e.g.,U.S. Pat. Nos. 5,082,670 and 5,618,531);

[0076] (f) injection, either subcutaneously, intravenously,intra-arterially, intramuscularly, or to other suitable site; or

[0077] oral administration, in capsule, liquid, tablet, pill, orprolonged release formulation.

[0078] In one embodiment of this invention, an active agent is delivereddirectly into the CNS, preferably to the brain ventricles, brainparenchyma, the intrathecal space or other suitable CNS location, mostpreferably intrathecally.

[0079] Alternatively, targeting therapies may be used to deliver theactive agent more specifically to certain types of cell, by the use oftargeting systems such as antibodies or cell specific ligands. Targetingmay be desirable for a variety of reasons, e.g. if the agent isunacceptably toxic, or if it would otherwise require too high a dosage,or if it would not otherwise be able to enter the target cells.

[0080] The active agents, which are peptides, can also be administeredin a cell based delivery system in which a DNA sequence encoding anactive agent is introduced into cells designed for implantation in thebody of the patient, especially in the spinal cord region. Suitabledelivery systems are described in U.S. Pat. No. 5,550,050 and publishedPCT Application Nos. WO 92/19195, WO 94/25503, WO 95/01203, WO 95/05452,WO 96/02286, WO 96/02646, WO 96/40871, WO 96/40959 and WO 97/12635.Suitable DNA sequences can be prepared synthetically for each activeagent on the basis of the developed sequences and the known geneticcode.

[0081] Exemplary methods for administering such muscle relaxantcompounds (e.g., so as to achieve sterile or aseptic conditions) will beapparent to the skilled artisan. Certain methods suitable foradministering compounds useful according to the present invention areset forth in Goodman and Gilman's The Pharmacological Basis ofTherapeutics, 7th Ed. (1985). The administration to the patient can beintermittent; or at a gradual, continuous, constant or controlled rate.Administration can be to a warm-blooded animal (e.g. a mammal, such as amouse, rat, cat, rabbit, dog, pig, cow or monkey); but advantageously isadministered to a human being. Administration occurs after generalanesthesia is administered. The frequency of administration normally isdetermined by an anesthesiologist, and typically varies from patient topatient.

[0082] The active agent is preferably administered in an therapeuticallyeffective amount. By a “therapeutically effective amount” or simply“effective amount” of an active compound is meant a sufficient amount ofthe compound to treat the desired condition at a reasonable benefit/riskratio applicable to any medical treatment. The actual amountadministered, and the rate and time-course of administration, willdepend on the nature and severity of the condition being treated.Prescription of treatment, e.g. decisions on dosage, timing, etc., iswithin the responsibility of general practitioners or spealists, andtypically takes account of the disorder to be treated, the condition ofthe individual patient, the site of delivery, the method ofadministration and other factors known to practitioners. Examples oftechniques and protocols can be found in Remington's ParmaceuticalSciences.

[0083] Dosage may be adjusted appropriately to achieve desired druglevels, locally or systemically. Typically the active agents of thepresent invention exhibit their effect at a dosage range from about0.001 mg/kg to about 250 mg/kg, preferably from about 0.01 mg/kg toabout 100 mg/kg of the active ingredient, more preferably from a bout0.05 mg/kg to about 75 mg/kg. A suitable dose can be administered inmultiple sub-doses per day. Typically, a dose or sub-dose may containfrom about 0.1 mg to about 500 mg of the active ingredient per unitdosage form. A more preferred dosage will contain from about 0.5 mg toabout 100 mg of active ingredient per unit dosage form. Dosages aregenerally initiated at lower levels and increased until desired effectsare achieved. In the event that the response in a subject isinsufficient at such doses, even higher doses (or effective higher dosesby a different, more localized delivery route) may be employed to theextent that patient tolerance permits. Continuous dosing over, forexample 24 hours or multiple doses per day are contemplated to achieveappropriate systemic levels of compounds.

[0084] For the treatment of pain, if the route of administration isdirectly to the CNS, the dosage contemplated is from about 1 ng to about100 mg per day, preferably from about 100 ng to about 10 mg per day,more preferably from about 1 μg to about 100 μg per day. If administeredperipherally, the dosage contemplated is somewhat higher, from about 100ng to about 1000 mg per day, preferably from about 10 μg to about 100 mgper day, more preferably from about 100 μg to about 10 mg per day. Ifthe conopeptide is delivered by continuous infusion (e.g., by pumpdelivery, biodegradable polymer delivery or cell-based delivery), then alower dosage is contemplated than for bolus delivery.

[0085] Advantageously, the compositions are formulated as dosage units,each unit being adapted to supply a fixed dose of active ingredients.Tablets, coated tablets, capsules, ampoules and suppositories areexamples of dosage forms according to the invention.

[0086] It is only necessary that the active ingredient constitute aneffective amount, i.e., such that a suitable effective dosage will beconsistent with the dosage form employed in single or multiple unitdoses. The exact individual dosages, as well as daily dosages, aredetermined according to standard medical principles under the directionof a physician or veterinarian for use humans or animals.

[0087] The pharmaceutical compositions will generally contain from about0.0001 to 99 wt. %, preferably about 0.001 to 50 wt. %, more preferablyabout 0.01 to 10 wt. % of the active ingredient by weight of the totalcomposition. In addition to the active agent, the pharmaceuticalcompositions and medicaments can also contain other pharmaceuticallyactive compounds. Examples of other pharmaceutically active compoundsinclude, but are not limited to, analgesic agents, cytokines andtherapeutic agents in all of the major areas of clinical medicine. Whenused with other pharmaceutically active compounds, the conopeptides ofthe present invention may be delivered in the form of drug cocktails. Acocktail is a mixture of any one of the compounds useful with thisinvention with another drug or agent. In this embodiment, a commonadministration vehicle (e.g., pill, tablet, implant, pump, injectablesolution, etc.) would contain both the instant composition incombination supplementary potentiating agent. The individual drugs ofthe cocktail are each administered in therapeutically effective amounts.A therapeutically effective amount will be determined by the parametersdescribed above; but, in any event, is that amount which establishes alevel of the drugs in the area of body where the drugs are required fora period of time which is effective in attaining the desired effects.

[0088] The practice of the present invention employs, unless otherwiseindicated, conventional techniques of chemistry, molecular biology,microbiology, recombinant DNA, genetics, immunology, cell biology, cellculture and transgenic biology, which are within the skill of the art.See, e.g., Maniatis et al., 1982; Sambrook et al., 1989; Ausubel et al.,1992; Glover, 1985; Anand, 1992; Guthrie and Fink, 1991; Harlow andLane, 1988; Jakoby and Pastan, 1979; Nucleic Acid Hybridization (B. D.Hames & S. J. Higgins eds. 1984); Transcription And Translation (B. D.Hames & S. J. Higgins eds. 1984); Culture Of Animal Cells (R. I.Freshney, Alan R. Liss, Inc., 1987); Immobilized Cells And Enzymes (IRLPress, 1986); B. Perbal, A Practical Guide To Molecular Cloning (1984);the treatise, Methods In Enzymology (Academic Press, Inc., N.Y.); GeneTransfer Vectors For Mammalian Cells (J. H. Miller and M. P. Calos eds.,1987, Cold Spring Harbor Laboratory); Methods In Enzymology, Vols. 154and 155 (Wu et al. eds.), Immunochemical Methods In Cell And MolecularBiology (Mayer and Walker, eds., Academic Press, London, 1987); HandbookOf Experimental Immunology, Volumes I-IV (D. M. Weir and C. C.Blackwell, eds., 1986); Riott, Essential Immunology, 6th Edition,Blackwell Scientific Publications, Oxford, 1988; Hogan et al.,Manipulating the Mouse Embryo, (Cold Spring Harbor Laboratory Press,Cold Spring Harbor, N.Y., 1986).

EXAMPLES

[0089] The present invention is described by reference to the followingExamples, which are offered by way of illustration and are not intendedto limit the invention in any manner. Standard techniques well known inthe art or the techniques specifically described below were utilized.

Example 1 Isolation of μ-Conopeptides

[0090] Crude venom was extracted from venom ducts (Cruz et al., 1976),and the components were purified as previously described (Cartier etal., 1996). The crude extract from venom ducts was purified by reversephase liquid chromatography (RPLC) using a Vydac C₁₈ semi-preparativecolumn (10×250 mm). Further purification of bioactive peaks was done ona Vydac C₁₈ analytical column (4.6×220 mm). The effluents were monitoredat 220 nm. Peaks were collected, and aliquots were assayed for activity.Throughout purification, HPLC fractions were assayed by means ofintracerebral ventricular (i.c.v.) injection into mice (Clark et al.,1981).

[0091] The amino acid sequence of the purified peptides were determinedby standard methods. The purified peptides were reduced and alkylatedprior to sequencing by automated Edman degradation on an AppliedBiosystems 477A Protein Sequencer with a 120A Analyzer (DNA/PeptideFacility, University of Utah) (Martinez et al., 1995; Shon et al.,1994).

[0092] In accordance with this method, the μ-conopeptides described as“isolated” in Table 1 were obtained. These μ-conopeptides, as well asthe other μ-conopeptides and the μ-conopeptide precursors set forth inTable 1 are synthesized as described in U.S. Pat. No. 5,670,622.

Example 2 Isolation of DNA Encoding μ-Conopeptides

[0093] DNA coding for μ-conopeptides was isolated and cloned inaccordance with conventional techniques using general procedures wellknown in the art, such as described in Olivera et al. (1996).Alternatively, cDNA libraries was prepared from Conus venom duct usingconventional techniques. DNA from single clones was amplified byconventional techniques using primers which correspond approximately tothe M13 universal priming site and the M13 reverse universal primingsite. Clones having a size of approximately 300-500 nucleotides weresequenced and screened for similarity in sequence to known μ-conotoxins.The DNA sequences and encoded propeptide sequences are set forth inTable 1. DNA sequences coding for the mature toxin can also be preparedon the basis of the DNA sequences set forth in Tablel. An alignment ofthe μ-conopeptides of the present invention is set forth in Table 2.TABLE 1 DNA and Amino Acid Sequences of μ-Conopeptides and PrecursorsName:     Ar3.1 Species:  arenatus Cloned:   Yes DNA Sequence:CAAGAAGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTCTTGACCATCTG (SEQ ID NO:1)TATGCTTCTGTTTCCCCTTACTGCTCTTCCGCTGGATGGGGATCAACCTGCAGACCGACCTGCAGAGCGTATGCAGGACGACTTTATAACTGAGCATCATCCCCTGTTTGATCCTGTCAAACGGTGTTGCGAGAGGCCATGCAACATAGGATGCGTACCTTGTTGTTAATGACCAGCTTTGTCATCGCGGCCTCATCAAGCGAATAAGTAAAACGATTGCAGT Translation:MMSKLGVFLTICMLLFPLTALPLDGDQPADRPAERMQDDFITEHHPLFDPVKRCCERPC (SEQ IDNO:2) NIGCVPCC Toxin Sequence:Cys-Cys-Xaa1-Arg-Xaa3-Cys-Asn-Ile-Gly-Cys-Val-Xaa3-Cys-Cys-{circumflexover ( )} (SEQ ID NO:3) Name:     Ak3.1 Species:  atlanticusCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGCTTCTGTTTCCAC (SEQ ID NO:4)TTACTGCTCTTCCGCTGGATGAAGATCAACCGGTACACCGACCTGCAGAGCGTATGCAGGACATTTCATCTGATCAACATCTCTTCTTTGATCTCATCAAACGGTGCTGCGAGTTGCCATGCGGGCCAGGCTTTTGCGTCCCTTGTTGCTGACATCAATAACGTGTTGATGACCAACTTTCTCGAG Translation:GSMMSKLGVLLTICLLLFPLTALPLDEDQPVHRPAERMQDISSDQHLFFDLIKRCCELPCG (SEQ IDNO:5) PGFCVPCC Toxin Sequence:Cys-Cys-Xaa1-Leu-Xaa3-Cys-Gly-Xaa3-Gly-Phe-Cys-Val-Xaa3-Cys-Cys-{circumflexover ( )} (SEQ ID NO:6) Name:     A3.1 Species:  aurisiacusCloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ ID NO:7)TTTGCTTCTGTTTCCCCTTACTGCTCTTCCGATGGATGGAGATCAATCTGTAGACCGACCTGAAGAGCGTATGCAGGACGACATTTCATCTGAGCAGCATCCCTTGTTTAATCAGAAAAGAATGTGTTGCGGCGAAGGCCGGAAATGCCCCAGCTATTTCAGAAACAGTCAGATTTGTCATTGTTGTTAAATGACAACGTGTCGATGACCAACTTCGTTATCACGACTAATGAATAAGTAAAACGATTGCAGT Translation:MMSKLGVLLTICLLLFPLTALPMDGDQSVDRPEERMQDDISSEQHPLFNQKRMCCGEGR (SEQ IDNO:8) KCPSYFRNSQICHCC Toxin Sequence:Met-Cys-Cys-Gly-Xaa1-Gly-Arg-Lys-Cys-Xaa3-Ser-Xaa5-Phe-Arg-Asn-Ser-Gln-Ile-Cys-His-(SEQ ID NO:9) Cys-Cys-{circumflex over ( )} Name:     A3.2Species:  aurisiacus Cloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTTTGCTTCTGTTTCCCC (SEQ IDNO:10) TTACTGCTCTTCCGATCGATGGAGATCAATCTGTAGACCGACCTGCAGAGCGTATGCAGGATGACATTTCATCTGAGCAGCATCGCTTGTTCAATCAGAAAAGAAGGTGCTGCCGGTGGCCATGCCCCCGACAAATCGACGGTGAATATTGTGGCTGTTGCCTTGGATGATAACCGTGTTGATGACCAACTTTCTCGAG Translation:GSMMSKLGVLLTICLLLFPLTALPIDGDQSVDRPAERMQDDISSEQHRLFNQKRRCCRW (SEQ IDNO:11) PCPRQIDGEYCGCCLG Toxin Sequence:Cys-Cys-Arg-Xaa4-Xaa3-Cys-Xaa3-Arg-Gln-Ile-Asp-Gly-Xaa1-Xaa5-Cys-Gly-Cys-Cys-Leu-#(SEQ ID NO:12) Name:     A3.3 Species:  aurisiacus Cloned:   Yes DNASequence: GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTACTTCTGTTTCCCC(SEQ ID NO:13) TTACTGCTTTTCCGATGGATGGAGATCAACCTGCAGACCAACCTGCAGATCGTATGCAGGACGACATTTCATCTGAGCAGTATCCCTTGTTTGATAAGAGACAAAAGTGTTGCACTGGGAAGAAGGGGTCATGCTCCGGCAAAGCATGCAAAAATCTCAAATGTTGCTCTGGACGATAACGTGTTGATGACCAACTTTCTCGAG Translation:GSMMSKLGVLLTICLLLFPLTAFPMDGDQPADQPADRMQDDISSEQYPLFDKRQKCCTG (SEQ IDNO:14) KKGSCSGKACKNLKCCSGR Toxin Sequence:Xaa2-Lys-Cys-Cys-Thr-Gly-Lys-Lys-Gly-Ser-Cys-Ser-Gly-Lys-Ala-Cys-Lys-Asn-Leu-Lys-Cys-(SEQ ID NO:15) Cys-Ser-# Name:     A3.4 Species:  aurisiacusCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGCTGACCATCTGTCTGCTTCTGTTTCCAC (SEQ IDNO:16) TTACTGCTGTTCCGCTGGATGGAGATCAACCTCTAGACCGACACGCGGAGCGTATGCATGATGGCATTTCACCTAAACGCCATCCCTGGTTTGATCCCGTCAAACGGTGTTGCAAGGTGCAATGCGAGTCTTGCACCCCTTGTTGCTAACGTGTTGATGACCAACTTTCTC GAGTranslation: GSMMSKLGVLLTICLLLFPLTAVPLDGDQPLDRHAERMHDGISPKRHPWFDPVKRCCKV(SEQ ID NO:17) QCESCTPCC Toxin Sequence:Cys-Cys-Lys-Val-Gln-Cys-Xaa1-Ser-Cys-Thr-Xaa3-Cys-Cys-{circumflex over( )} (SEQ ID NO:18) Name:     Bn3.1 Species:  bandanus Cloned:   Yes DNASequence: GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTATGCTTCTGTTTCCCC(SEQ ID NO:19) TCACTGCTCTTCCGATGGATGGAGATCAACCTGCAGACCGACCTGCAGAGCGTAGTCAGGACGTTTCATCTGAACAGCATCCCTTGTTTGATCCCGTCAAACGGTGTTGCAACTGGCCATGCTCCATGGGATGCATCCCTTGTTGCTACTATTAATAACGTGTTGATGAC CAACTTTCTCGAGTranslation: GSMMSKLGVLLTICMLLFPLTALPMDGDQPADRPAERSQDVSSEQHPLFDPVKRCCNW(SEQ ID NO:20) PCSMGCIPCCYY Toxin Sequence:Cys-Cys-Asn-Xaa4-Xaa3-Cys-Ser-Met-Gly-Cys-Ile-Xaa3-Cys-Cys-Xaa5-Xaa5-{circumflexover ( )} (SEQ ID NO:21) Name:     Bt3.1 Species:  betulinusCloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCTTCTG (SEQ ID NO:22)TCTGCTTCTGTTTCCCCTGACTGCTCTTCCGCTGGATGAAGATCAACCTGCAGACCGACCTGCAGAGCGTATGCAGGACATTTCATCTGAACAGCATCCCTTGTTTGATCCCGTCAAACGGTGTTGCGAATTGCCATGCCATGGATGCGTCCCTTGTTGCTGGCCTTAATAACGTGTGGATGACCAACTGTGTTATCACGGCCACGTCAAGTGTCTAATGAATAAGT AAAATGATTGCAGTTranslation:MMSKLGVLLTFCLLLFPLTALPLDEDQPADRPAERMQDISSEQHPLFDPVKRCCELPCHG (SEQ IDNO:23) CVPCCWP Toxin Sequence:Cys-Cys-Xaa1-Leu-Xaa3-Cys-His-Gly-Cys-Val-Xaa3-Cys-Cys-Xaa4-Xaa3-{circumflexover ( )} (SEQ ID NO:24) Name:     Bt3.2 Species:  betulinusCloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCTTCTG (SEQ ID NO:25)TCTGCTTCTGTTTCCCCTGACTGCTCTTCCGCTGGATGAAGATCAACCTGCAGACCGACATGCAGAGCGTATGCAGGACATTTCACCTGAACAGCATCCCTCGTTTGATCCCGTCAAACGGTGTTGCGGGCTGCCATGCAATGGATGCGTCCCTTGTTGCTGGCCTTCATAACGTGTGGACGACCAACTTTGTTATCACGGCCACGTCAAGTGTCTGATGAATAAGTA AAACGATTGCAGTTranslation: MMSKLGVLLTFCLLLFPLTALPLDEDQPADRHAERMQDISPEQHPSFDPVKRCCGLPCN(SEQ ID NO:26) GCVPCCWPS Toxin Sequence:Cys-Cys-Gly-Leu-Xaa3-Cys-Asn-Gly-Cys-Val-Xaa3-Cys-Cys-Xaa4-Xaa3-Ser-{circumflexover ( )} (SEQ ID NO:27) ------------------------------- Name:     Bt3.3Species:  betulinus Cloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTTTAAACTGGGAGTCTTGTTGACCATCTA (SEQ ID NO:28)TATGCTTCTGTTTCCCTTTACTGCTCTTCCGCTGGATGGAGATCAACCTGCAGACCAACCTCTAGAGCGCATGCAGTATGACATGTTACGTGCAGTGAATCCCTGGTTTGATCCCGTCAAAAGGTGCTGCTCGAGGAACTGCGCAGTATGCATCCCTTGTTGCCCGAATTGGCCAGCTTGATTATCGCGGCCAAGAGTCTAATGAATAAGTAAAACGATTGCAGT Translation:MMFKLGVLLTIYMLLFPFTALPLDGDQPADQPLERMQYDMLRAVNPWFDPVKRCCSR (SEQ ID NO:29)NCAVCIPCCPNWPA Toxin Sequence:Cys-Cys-Ser-Arg-Asn-Cys-Ala-Val-Cys-Ile-Xaa3-Cys-Cys-Xaa3-Asn-Xaa4-Xaa3-Ala-{circumflexover ( )} (SEQ ID NO:30) Name:     Bu3.1 Species:  bullatusCloned:   Yes DNA Sequence:CAAGAAGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ ID NO:31)TCTGCTTCTGTTTCCCCTTTTTGCTCTTCCGCAGGATGGAGATCAACCTGCAGACCGACCTGCAGAGCGTATGCAGGACGACATTTCATCTGAGCAGAATTCCTTGCTTGAGAAGAGAGTTACTGACAGGTGCTGCAAAGGGAAGAGGGAATGCGGCAGATGGTGCAGAGATCACTCGCGTTGTTGCGGTCGACGATAAGCTGTTGATGACCAGCTTTGTTATCACGGCTACATCAAGTGTCTAGTGAATAAGTAAAATGATTGCAGT Translation:MMSKLGVLLTICLLLFPLFALPQDGDQPADRPAERMQDDISSEQNSLLEKRVTDRCCKG (SEQ IDNO:32) KRECGRWCRDHSRCCGRR Toxin Sequence:Val-Thr-Asp-Arg-Cys-Cys-Lys-Gly-Lys-Arg-Xaa1-Cys-Gly-Arg-Xaa4-Cys-Arg-Asp-His-Ser-(SEQ ID NO:33) Arg-Cys-Cys-# Name:     Bu3.1A Species:  bullatusCloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ ID NO:34)TCTGCTTCTGTTTCCCCTTTTTGCTCTTCGGCAGGATGGAGATCAACCTGCAGACCGACCTGCAGAGCGTATGCAGGATGACATTTCATCTGAGCAGAATCCCTTGCTTGAGAAGAGAGTTGGTGACAGGTGCTGCAAAGGGAAGAGGGGGTGCGGCAGATGGTGCAGAGATCACTCACGTTGTTGCGGTCGACGATAACGTGTTGATGACCAGCTTTGTTATCACGGCTACATCAAGTGTCTTAGTGATTAAGTAAAACGATTGCAGT Translation:MMSKLGVLLTICLLLFPLFALRQDGDQPADRPAERMQDDISSEQNPLLEKRVGDRCCKG (SEQ IDNO:35) KRGCGRWCRDHSRCCGRR Toxin Sequence:Val-Gly-Asp-Arg-Cys-Cys-Lys-Gly-Lys-Arg-Gly-Cys-Gly-Arg-Xaa4-Cys-Arg-Asp-His-Ser-(SEQ ID NO:36) Arg-Cys-Cys-# Name:     Bu3.2 Species:  bullatusCloned:   Yes DNA Sequence:CAAGAAGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ ID NO:37)TCTGCTTCTGTTTCCCCTTTTTGCTCTTCCGCAGGATGGAGATCAACCTGCAGACCGACCTGCAGAGCGTATGCAGGACGACATTTCATCTGAGCAGAATCCCTTGCTTGAGAAGAGAGTTGGTGAAAGGTGCTGCAAAAACGGGAAGAGGGGGTGCGGCAGATGGTGCAGAGATCACTCACGTTGTTGCGGTCGACGATAACGTGTTGATGACCGAGGCTTTCGTTATCACGGCTACATCAAGTGTCTAGTGAATAAGTAAAACGATTGCAGT Translation:MMSKLGVLLTICLLLFPLFALPQDGDQPADRPAERMQDDISSEQNPLLEKRVGERCCKN (SEQ IDNO:38) GKRGCGRWCRDHSRCCGRR Toxin Sequence:Val-Gly-Xaa1-Arg-Cys-Cys-Lys-Asn-Gly-Lys-Arg-Gly-Cys-Gly-Arg-Xaa4-Cys-Arg-Asp-His-(SEQ ID NO:39) Ser-Arg-Cys-Cys-# Name:     Bu3.3 Species:  bullatusCloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ ID NO:40)TCTGCTTCTGTTTCCCCTTTTTGCTCTTCCGCAGGACGGAGATCAACCTGCAGACCGACCTGCAGAGCGTATGCAGGACGACCTTTCATCTGAGCAGCATCCCTTGTTTGAGAAGAGAATTGTTGACAGGTGCTGCAACAAAGGGAACGGGAAGAGGGGGTGCAGCAGATGGTGCAGAGATCACTCACGTTGTTGCGGTCGACGATGAACTGTTGATGACCGAGGCTTTGGTTATCACGGCTACATCAAGTGTCTAGTGAATAAGTAAAACGATTGCAGT Translation:MMSKLGVLLTICLLLFPLFALPQDGDQPADRPAERMQDDLSSEQHPLFEKRIVDRCCNK (SEQ IDNO:41) GNGKRGCSRWCRDHSRCCGRR Toxin Sequence:Ile-Val-Asp-Arg-Cys-Cys-Asn-Lys-Gly-Asn-Gly-Lys-Arg-Gly-Cys-Ser-Arg-Xaa4-Cys-Arg-(SEQ ID NO:42) Asp-His-Ser-Arg-Cys-Cys-# Name:     Bu3.4Species:  bullatus Cloned:   Yes DNA Sequence:CAAGAAGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ ID NO:43)TCTGCTTCTGTTTCCCCTTTTTGCTCTTCCGCAGGATGGAGATCAACCTGCAGACCGACCTGCTGAGCGTATGCAGGACGACATTTCATCTGAGCGGAATCCCTTGTTTGAGAAGAGCGTTGGTTTATATTGCTGCCGACCCAAACCCAACGGGCAGATGATGTGCGACAGATGGTGCGAAAAAAACTCACGTTGTTGCGGTCGACGATAATGTGTTGATGACCAGCTTTGTTATCAAGGCTACATCAAGTATCTAGTGAATAAGTAAAACGATTGCAGT Translation:MMSKLGVLLTICLLLFPLFALPQDGDQPADRPAERMQDDISSERNPLFEKSVGLYCCRPK (SEQ IDNO:44) PNGQMMCDRWCEKNSRCCGRR Toxin Sequence:Val-Gly-Leu-Xaa5-Cys-Cys-Arg-Xaa3-Lys-Xaa3-Asn-Gly-Gln-Met-Met-Cys-Asp-Arg-Xaa4-(SEQ ID NO:45) Cys-Xaa1-Lys-Asn-Ser-Arg-Cys-Cys-#------------------------------- Name:     Bu3.5 Species:  bullatusCloned:   Yes DNA Sequence:CAAGAAGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTTTTGTTGACCATCTG (SEQ ID NO:46)TCTGCTTCTGTTTCCCCTTACTGCTCTTCCGATGGATGGAGATCAATCTGTAGACCGACCTGCAGAACGTATGCAGGACGACCTTTCATCTGAGCAGCATCCCTTGTTTGTTCAGAAAAGAAGGTGTTGCGGCGAAGGCTTGACATGCCCCAGATATTGGAAAAACAGTCAGATTTGTGCTTGTTGTTAAATGACAACGTGTCGATGACCAACTTCGGTATCACGACTACGCCAAGTGTCTAATGAATAAGTAAAACGATTGCAGT Translation:MMSKLGVLLTICLLLFPLTALPMDGDQSVDRPAERMQDDLSSEQHPLFVQKRRCCGEGL (SEQ IDNO:47) TCPRYWKNSQICACC Toxin Sequence:Arg-Cys-Cys-Gly-Xaa1-Gly-Leu-Thr-Cys-Xaa3-Arg-Xaa5-Xaa4-Lys-Asn-Ser-Gln-Ile-Cys-Ala-(SEQ ID NO:48) Cys-Cys-{circumflex over ( )} Name:     Bu3.5ASpecies:  bullatus Cloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ ID NO:49)TCTGCTTCTGTTTCCCCTTTTTGCTCTTCCGCAGGATGGAGATCAACCTGCAGACCGACCTGCTGAGCGTATGCAGGACGACATTTCATCTGAGCAGGATCCCTTGTTTGTTCAGAAAAGAAGGTGTTGCGGCGAAGGCTTGACATGCCCCAGATATTGGAAAAACAGTCAGATTTGTGCTTGTTGTTAAATGACAACGTGTGATGACCAACTTCGGTATCACGACTACGCCAAGTGTCTAATGAATAAGTAAAACGATTGCAGT Translation:MMSKLGVLLTICLLLFPLFALPQDGDQPADRPAERMQDDISSEQDPLFVQKRRCCGEGL (SEQ IDNO:50) TCPRYWKNSQICACC Toxin Sequence:Arg-Cys-Cys-Gly-Xaa1-Gly-Leu-Thr-Cys-Xaa3-Arg-Xaa5-Xaa4-Lys-Asn-Ser-Gln-(SEQ ID NO:51) Ile-Cys-Ala-Cys-Cys-{circumflex over ( )} Name:     Cp3.1Species:  capitaneus Cloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGGTGACCATCTGCCTGCTTCTGTTTCCC (SEQ ID NO:52)CTTGCTGCTTTTCCACTGGATGGAAATCAACCTGCAGACCACCCTGCAAAGCGTACGCAAGATGACAGTTCAGCTGCCCTGATCAATACCTGGATTGATCATTCCCATTCTTGCTGCAGGGACTGCGGTGAAGATTGTGTTGGTTGTTGCCGGTAACGTGTTGATGACCAA CTTTCTCGAGTranslation: GSMMSKLGVLVTICLLLFPLAAFPLDGNQPADHPAKRTQDDSSAALINTWIDHSHSCCR(SEQ ID NO:53) DCGEDCVGCCR Toxin Sequence:Ser-Cys-Cys-Arg-Asp-Cys-Gly-Xaa1-Asp-Cys-Val-Gly-Cys-Cys-Arg-{circumflexover ( )} (SEQ ID NO:54) Name:     Ca3.1 Species:  caracteristicusCloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ ID NO:55)TCTGCTTCTGTTTCCCCTTACTGCTCTTCCAATGGATGGAGATCAACCTGCAGACCAACCTGCAGATCGTATGCAGGACGACATTTCATCTGAGCAGTATCCCTTGTTTGATATGAGAAAAAGGTGTTGCGGCCCCGGCGGTTCATGCCCCGTATATTTCAGAGACAATTTTATTTGTGGTTGTTGTTAAATGACAACGTGTCGATGACCAACTTCATTATCACGACTACGCCAAGTGTCTAATGAATAAGTAAAATGATTGCAGT Translation:MMSKLGVLLTICLLLFPLTALPMDGDQPADQPADRMQDDISSEQYPLFDMRKRCCGPG (SEQ IDNO:56) GSCPVYFRDNFICGCC Toxin Sequence:Cys-Cys-Gly-Xaa3-Gly-Gly-Ser-Cys-Xaa3-Val-Xaa5-Phe-Arg-Asp-Asn-Phe-Ile-Cys-Gly-Cys-(SEQ ID NO:57) Cys-{circumflex over ( )} Name:     Ca3.2Species:  caracteristicus Cloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ ID NO:58)TCTGCTTCTGTTTCCCCTTACTGCTCTTCCGATGGATGGAGATGAACCTGCAAACCGACCTGTCGAGCGTATGCAGGACAACATTTCATCTGAGCAGTATCCCTTGTTTGAGAAGAGACGAGATTGTTGCACTCCGCCGAAGAAATGCAAAGACCGACAATGCAAACCCCAGAGATGTTGCGCTGGACGATAACGTGTTGATGACCAACTTTATCACGGCTACGTCAAGTGTTTAGTGAATAAGTAAAATGATTGCAGT Translation:MMSKLGVLLTICLLLFPLTALPMDGDEPANRPVERMQDNISSEQYPLFEKRRDCCTPPK (SEQ IDNO:59) KCKDRQCKPQRCCAGR Toxin Sequence:Arg-Asp-Cys-Cys-Thr-Xaa3-Xaa3-Lys-Lys-Cys-Lys-Asp-Arg-Gln-Cys-Lys-Xaa3-Gln-Arg-Cys-(SEQ ID NO:60) Cys-Ala-# Name:     Ca3.3 Species:  caracteristicusCloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ ID NO:61)TCTGCTTCTGTTTCCCCTTACTGCTCTTCCACTGGATGGAGATCAACCTGCAGATCAATCTGCAGAGCGACCTGCAGAGCGTACGCAGGACGACATTCAGCAGCATCCGTTATATGATCCGAAAAGAAGGTGTTGCCGTTATCCATGCCCCGACAGCTGCCACGGATCTTGCTGCTATAAGTGATAACATGTTGATGGCCAGCTTTGTTATCACGGCCACGTCAAGTGTCTTAATGAATAAGTAAAACGATTGCAGT Translation:MMSKLGVLLTICLLLFPLTALPLDGDQPADQSAERPAERTQDDIQQHPLYDPKRRCCRY (SEQ IDNO:62) PCPDSCHGSCCYK Toxin Sequence:Arg-Cys-Cys-Arg-Xaa5-Xaa3-Cys-Xaa3-Asp-Ser-Cys-His-Gly-Ser-Cys-Cys-Xaa5-Lys-{circumflexover ( )} (SEQ ID NO:63) Name:     Ca3.4 Species:  caracteristicusCloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGCCTTGTTGACCATCT (SEQ ID NO:64)GTCTACTTCTGTTTTCCCTTACTGCTGTTCCGCTGGATGGAGATCAACATGCAGACCAACCTGCACAGCGTCTGCAGGACCGCATTCCAACTGAAGATCATCCCTTATTTGATCCCAACAAACGGTGTTGCCCGCCGGTGGCATGCAACATGGGATGCAAGCCTTGTTGTGGATGACCAGCTTTGTTATCGCGGTCTTCATGAAGTGTCTTAATGAATAAGTAAAAT GATTGCAGTTranslation: MMSKLGALLTICLLLFSLTAVPLDGDQHADQPAQRLQDRIPTEDHPLFDPNKRCCPVA(SEQ ID NO:65) CNMGCKPCCG Toxin Sequence:Cys-Cys-Xaa3-Xaa3-Val-Ala-Cys-Asn-Met-Gly-Cys-Lys-Xaa3-Cys-Cys-# (SEQ IDNO:66) Name:     Ca3.5 Species:  caracteristicus Cloned:   Yes DNASequence: CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGCCTTGTTGACCATCT (SEQID NO:67) GTCTACTTCTGTTTTCCCTAACTGCTGTTCCGCTGGATGGAGATCAACATGCAGACCAACCTGCAGAGCGTCTGCATGACCGCCTTCCAACTGAAAATCATCCCTTATATGATCCCGTCAAACGGTGTTGCGATGATTCGGAATGCGACTATTCTTGCTGGCCTTGCTGTATGTTTGGATAACCTTTGTTATCGCGGCCTCATCAAGTGTCTAATGAATAAGTAAAAC GATTGCAGTTranslation: MMSKLGALLTICLLLFSLTAVPLDGDQHADQPAERLHDRLPTENHPLYDPVKRCCDDSE(SEQ ID NO:68) CDYSCWPCCMFG Toxin Sequence:Cys-Cys-Asp-Asp-Ser-Xaa1-Cys-Asp-Xaa5-Ser-Cys-Xaa4-Xaa3-Cys-Cys-Met-Phe-#(SEQ ID NO:69) Name:     Ca3.6 Species:  caracteristicus Cloned:   YesDNA Sequence: GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGCTTCTGTTTCCCC(SEQ ID NO:70) TTACTGCTGTTCCGCTGGATGGAGATCAACCTGCAGACCGACCTGCAGAGCGTAAGCAGGACGTTTCATCTGAACAGCATCCCTTCTTTGATCCCGTCAAACGGTGTTGCCGCCGGTGTTACATGGGATGCATCCCTTGTTGCTTTTAACGTGTTGATGACCAACTTTCTC GAGTranslation: GSMMSKLGVLLTICLLLFPLTAVPLDGDQPADRPAERKQDVSSEQHPFFDPVKRCCRRC(SEQ ID NO:71) YMGCIPCCF Toxin Sequence:Cys-Cys-Arg-Arg-Cys-Xaa5-Met-Gly-Cys-Ile-Xaa3-Cys-Cys-Phe-{circumflexover ( )} (SEQ ID NO:72) Name:     Cr3.1 Species:  circumcisusCloned:   Yes DNA Sequence:CAAGAAGGATCGATAGCAGTTCATGATGTCTAAACTGGGGGTATTGTTGACCATCT (SEQ ID NO:73)GTCTGCTTCTGTTTCCCCTTACTGCTCTTCCAATGGATGGAGATCAACCTGCAGACCAACCTGCAGATCGTATGCAGGACGACATTTCATCTGAGCAGTATCCCTTGTTTGATAAGAGACGAAAGTGTTGCGGCAAAGACGGGCCATGCCCCAAATATTTCAAAGACAATTTTATTTGTGGTTGTTGTTAAATGACAACGTGTCGATGACCAACTTCGTTATCACGATTCGCCAAGTGTCTTAATGAATAAGTAAAATGATTGCAGT Translation:MMSKLGVLLTICLLLFPLTALPMDGDQPADQPADRMQDDISSEQYPLFDKRRKCCGKD (SEQ IDNO:74) GPCPKYFKDNFICGCC Toxin Sequence:Arg-Lys-Cys-Cys-Gly-Lys-Asp-Gly-Xaa3-Cys-Xaa3-Lys-Xaa5-Phe-Lys-Asp-Asn-Phe-Ile-Cys-(SEQ ID NO:75) Gly-Cys-Cys-{circumflex over ( )} Name:     Da3.1Species:  dalli Cloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGCCTTGTTGACCATCT (SEQ ID NO:76)GTCTACTTCTGTTTTCCCTAACTGCTGTTCCGCTGGATGGAGATCAACATGCAGACCAACCTGCAGAGCGTCTGCAGGACCGCCTTCCAACTGAAAATCATCCCTTATATGATCCCGTCAAACGGTGTTGCGATGATTCGGAATGCGACTATTCTTGCTGGCCTTGCTGTATTTTATCATAACCTTTGTTATCGCGGCCTCATCAAGTGTCAAATGAATAAGTAAAAT GATTGCAGTTranslation: MMSKLGALLTICLLLFSLTAVPLDGDQHADQPAERLQDRLPTENHPLYDPVKRCCDDSE(SEQ ID NO:77) CDYSCWPCCIILS Toxin Sequence:Cys-Cys-Asp-Asp-Ser-Xaa1-Cys-Asp-Xaa5-Ser-Cys-Xaa4-Xaa3-Cys-Cys-Ile-Leu-Ser-{circumflexover ( )} (SEQ ID NO:78) Name:     Da3.2 Species:  dalli Cloned:   YesDNA Sequence: CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATTTG(SEQ ID NO:79) TCTACTTCTGTTTCCCCTTACTGCTGTTCCACTGGATGGAGATCAGCCTGCAGACCGACCTGCAGAGCGTATGCAGGACGGCATTTCATCTGAACATCATCCATTTTTTGATTCCGTCAAAAAGAAACAACAGTGTTGCCCGCCGGTGGCATGCAACATGGGATGCGAGCCTTGTTGTGGATGACCAGCTTTGTTATCGCGGCTCATGAAGTGTCCTAATGAATAAGTAAAACGATTGCAGT Translation:MMSKLGVLLTICLLLFPLTAVPLDGDQPADRPAERMQDGISSEHHPFFDSVKKKQQCCP (SEQ IDNO:80) PVACNMGCEPCCG Toxin Sequence:Xaa2-Gln-Cys-Cys-Xaa3-Xaa3-Val-Ala-Cys-Asn-Met-Gly-Cys-Xaa1-Xaa3-Cys-Cys-#(SEQ ID NO:81) Name:     Da3.3 Species:  dalli Cloned:   Yes DNASequence: CAAGAAGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGATCATATG (SEQID NO:82) TCTATTTCTGTTTCCCCTTACTGCTGTTCAGCTCAATGGAGATCAGCCTGCAGACCAATCTGCAGAGCGTATGCAGGACAAAATTTCATCTGAACATCATCCCTTTTTTGATCCCGTCAAACGTTGTTGCAACGCGGGGTTTTGCCGCTTCGGATGCACGCCTTGTTGTTGGTGACCAGCTTTGTTATCGCGGCCTCATCAAGTGTCTAATGAATAAGTAAAATGATTG CAGTTranslation:MMSKLGVLLIICLFLFPLTAVQLNGDQPADQSAERMQDKISSEHHPFFDPVKRCCNAGFC (SEQ IDNO:83) RFGCTPCCW Toxin Sequence:Cys-Cys-Asn-Ala-Gly-Phe-Cys-Arg-Phe-Gly-Cys-Thr-Xaa3-Cys-Cys-Xaa4-{circumflexover ( )} (SEQ ID NO:84) Name:     Di3.1 Species:  distans Cloned:   YesDNA Sequence: CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGCTGACCATCTT(SEQ ID NO:85) TCTGCTTCTGTTTCCCCTTACTGCTGTTCCGCTGGATGGAGATCAACCCGCAGACGGACTTGCAGAGCGCATGCAGGACGACAGTTCAGCTGCACTGATTAGAGACTGGCTTCTTCAAACCCGACAGTGTTGTGTGCATCCATGCCCATGCACGCCTTGCTGTAGATGACCAGCTTTGTCATCGCGGCTACGTCAAGTATCTAATGAATAAGTAAGTAAAACGATTG CAGTTranslation: MMSKLGVLLTIFLLLFPLTAVPLDGDQPADGLAERMQDDSSAALIRDWLLQTRQCCVHP(SEQ ID NO:86) CPCTPCCR Toxin Sequence:Xaa2-Cys-Cys-Val-His-Xaa3-Cys-Xaa3-Cys-Thr-Xaa3-Cys-Cys-Arg-{circumflexover ( )} (SEQ ID NO:87) Name:     E3.1 Species:  ermineus Cloned:   YesDNA Sequence: ACCTCAAGAGGGATCGATCGCAGTTCATGATGTCTAAACTGGGAGCCTTGTTGACC(SEQ ID NO:88)ATCTGTCTGCTTCTGTTTCCCATTACTGCTCTTCTGATGGATGGAGATCAGCCTGCAGACCGACCTGCAGAGCGTACGGAGGATGACATTTCATCTGACTACATTCCCTGTTGCAGTTGGCCATGCCCCCGATACTCCAACGGTAAACTTGTTTGTTTTTGTTGCCTTGGATGATAATGTGTTGATGACCAACTTTGTTATCACGGCTACGTCAAGTGTCTACTGAATAAGTAAAATGATTGCAGTA Translation:MMSKLGALLTICLLLFPITALLMDGDQPADRPAERTEDDISSDYIPCCSWPCPRYSNGKL (SEQ IDNO:89) VCFCCLG Toxin Sequence:Cys-Cys-Ser-Xaa4-Xaa3-Cys-Xaa3-Arg-Xaa5-Ser-Asn-Gly-Lys-Leu-Val-Cys-Phe-Cys-Cys-(SEQ ID NO:90) Leu-# Name:     Ge3.2 Species:  generalis Cloned:   YesDNA Sequence: GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGGTTCTGTTTCCCC(SEQ ID NO:91) TTACTGCTCTTCCACTGGATGGAGAACAACCTGTAGACCGACATGCCGAGCATATGCAGGATGACAATTCAGCTGCACAGAACCCCTGGGTTATTGCCATCAGACAGTGTTGCACGTTCTGCAACTTTGGATGCCAACCTTGTTGCCTCACCTGATAACGTGTTGATGAC CAACTTTCTCGAGTranslation: GSMMSKLGVLLTICLVLFPLTALPLDGEQPVDRHAEHMQDDNSAAQNPWVIAIRQCCTF(SEQ ID NO:92) CNFGCQPCCLT Toxin Sequence:Xaa2-Cys-Cys-Thr-Phe-Cys-Asn-Phe-Gly-Cys-Gln-Xaa3-Cys-Cys-Leu-Thr-{circumflexover ( )} (SEQ ID NO:93) Name:     Ge3.3 Species:  generalisCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGGTTCTGTTTCCCC (SEQ IDNO:94) TTACTGCTCTTCCACTGGATGGAGAACAACCTGTAGACCGACATGCCGAGCATATGCAGGATGACAATTCAGCTGCACAGAACCCCTGGGTTATTGCCATCAGACAGTGTTGCACGTTCTGCAACTTTGGATGCCAGCCTTGTTGCGTCCCCTGATAACGTGTTGATGAC CAACTTTCTCGAGTranslation: GSMMSKLGVLLTICLVLFPLTALPLDGEQPVDRHAEHMQDDNSAAQNPWVIAIRQCCTF(SEQ ID NO:95) CNFGCQPCCVP Toxin Sequence:Xaa2-Cys-Cys-Thr-Phe-Cys-Asn-Phe-Gly-Cys-Gln-Xaa3-Cys-Cys-Val-Xaa3-{circumflexover ( )} (SEQ ID NO:96) Name:     μ-GIIIA Species:  geographusCloned:   Yes DNA Sequence:GTCGACTCTAGAGGATCCGACAACAAAGAGTCAACCCCACTGCCACGTCAAGAGCG (SEQ ID NO:97)AAGCGCCACAGCTAAGACAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGCTTCTGTTTCCCCTTACTGCTCTTCCGATGGATGGAGATGAACCTGCAAACCGACCTGTCGAGCGTATGCAGGACAACATTTCATCTGAGCAGTATCCCTTGTTTGAGAAGAGACGAGATTGTTGCACTCCGCCGAAGAAATGCAAAGACCGACAATGCAAACCCCAGAGATGTTGCGCTGGACGATAACGTGTTGATGACCAACTTTATCACGGCTACGTCAAGTGTTTAGTGAATAAGTAAAATGATTGCAGTCTTGCTCAGATTTGCTTTTGTGTTTTGGTCTAAAGATCAATGACCAAACCGTTGTTTTGATGCGGATTGTCATATATTTCTCGATTCCAATCCAACACTAGATGATTTAATCACGATAGATTAATTTTCTATCAATGCCTTGATTTTTCGTCTGTCATATCAGTTTTGTTTATATTTATTTTTTCGTCACTGTCTACACAAACGCATGCATGCACGCATGCACGCACACACGCACGCACGCTCGCACAAACATGCGCGCGCACGCACACACACACACACACACACAAACACACACACAAGCAATCACACAATTATTGACATTATTTATTTATTCATTGATGTATTTGTTATTCGTTTGCTTGTTTTTAGAATAGTTTGAGGCCGTCTTTTTGGATTTATTTGAACTGCTTTATTGTATACGAGTACTTCGTGCTTTGAAACACTGCTGAAAATAAAACAAACACT GACGTAGCTranslation: MMSKLGVLLTICLLLFPLTALPMDGDEPANRPVERMQDNISSEQYPLFEKRRDCCTPPK(SEQ ID NO:98) KCKDRQCKPQRCCAGR Toxin Sequence:Arg-Asp-Cys-Cys-Thr-Xaa3-Xaa3-Lys-Lys-Cys-Lys-Asp-Arg-Gln-Cys-Lys-Xaa3-Gln-Arg-Cys-(SEQ ID NO:99) Cys-Ala-# Name:     μ-GIIIB Species:  geographusIsolated: Yes Cloned:   Yes DNA Sequence:GGCCAGACGACAACAAAGAGTCAACCCCACTGCCACGTCAAGAGCGAAGCGCCAC (SEQ ID NO:100)AGCTAAGACAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGCTTCTGTTTCCCCTTACTGCTCTTCCGATGGATGGAGATGAACCTGCAAACCGACCTGTCGAGCGTATGCAGGACAACATTTCATCTGAGCAGTATCCCTTGTTTGAGAAGAGACGAGATTGTTGCACTCCGCCGAGGAAATGCAAAGACCGACGATGCAAACCCATGAAATGTTGCGCTGGACGATAACGTGTTGATGACCAACTTTATCACGGCTAGCTCAGTGTTTAGTGAATAAGTAAAATGATTGCAGTCTTGCTCAGATTGCTTTTGTGTTTTGGTCTAAGATCAATGACCAAACCGTTGTTTTGATGCGGATTGTCATATATTTCTCGATTCCAATCCAACACTAGATGATTTAATCACGATAGATTAATTTTCTATCAATGCCTTGATTTTTCGTCTGTCATATCAGTTTTGTTTATATTTATTTTTTCGTCACTGTCTACACAAACGCATGCATGCACGCATGCACGCACACACGCACGCACGCTCGCACAAACATGCGCGCGCACGCACACACACACACACACACAAACACACACACGAAGCAATCACACAATTAGTTGACATTATTTATTTATTCATTGATGTATTTGTTATTCGTTTGCTTGTTTTTAGAATAGTTTGAGGCCGTCTTTTTGGATTTATTTGAACTGCTTTATTGTATACGAGTACTTCGTGCTTTGAAACACTGCTGAAAATAAAACAAACACTGACGTAGCAAAA AAAAAAATranslation:MMSKLGVLLTICLLLFPLTALPMDGDEPANRPVERMQDNISSEQYPLFEKRRDCCTPPRK (SEQ IDNO:101) CKDRRCKPMKCCAGR Toxin Sequence:Arg-Asp-Cys-Cys-Thr-Xaa3-Xaa3-Arg-Lys-Cys-Lys-Asp-Arg-Arg-Cys-Lys-Xaa3-Met-Lys-Cys-(SEQ ID NO:102) Cys-Ala-# Name:     μ-GIIIC Species:  geographusIsolated: Yes Toxin Sequence:Arg-Asp-Cys-Cys-Thr-Xaa3-Xaa3-Lys-Lys-Cys-Lys-Asp-Arg-Arg-Cys-Lys-Xaa3-Leu-Lys-Cys-(SEQ ID NO:103) Cys-Ala-# Name:     Gm3.1 Species:  gloriamarisCloned:   Yes DNA Sequence:CTCACTATAGGAATTCGAGCTCGGTACACGGGATCGATAGCAGTTCATGATGTCTAA (SEQ IDNO:104) ACTGGGAGCCTTGTTGACCATCTGTCTACTTCTGTTTTCCCTAACTGCTGTTCCGCTGGATGGAGATCAACATGCAGACCAACCTGCAGAGCGTCTGCATGACCGCCTTCCAACTGAAAATCATCCCTTATATGATCCCGTCAAACGGTGTTGCGATGATTCGGAATGCGACTATTCTTGCTGGCCTTGCTGTATGTTTGGATAACCTTTGTTATCGCGGCCTCGATAAGTGTCTAATGAATAAGTAAAACGATTGCAGTAGGC Translation:MMSKLGALLTICLLLFSLTAVPLDGDQHADQPAERLHDRLPTENHPLYDPVKRCCDDSE (SEQ IDNO:105) CDYSCWPCCMFG Toxin Sequence:Cys-Cys-Asp-Asp-Ser-Xaa1-Cys-Asp-Xaa5-Ser-Cys-Xaa4-Xaa3-Cys-Cys-Met-Phe-#(SEQ ID NO:106) Name:     Gm3.2 Species:  gloriamaris Cloned:   Yes DNASequence: GTTCATGATGTCTAAACTGGGAGTCTTGTTGATCATCTGTCTACTTCTGTTTCCCCTT(SEQ ID NO:107) ACTGCTGTTCCGCTGGATGGAGATCAACCTGCAGACCGATATGCAGAGCGTATGCAGGACGACATTTCATCTGAACATCATCCCATGTTTGATGCCGTCAGAGGGTGTTGCCATCTGTTGGCATGCCGCTTCGGATGCTCGCCTTGTTGTTGGTGATCAGCTTTGTTATCGCGGCCTCATCAAGTGACTCTAATGCAAA Translation:MMSKLGVLLIICLLLFPLTAVPLDGDQPADRYAERMQDDISSEHHPMFDAVRGCCHLLA (SEQ IDNO:108) CRFGCSPCCW Toxin Sequence:Gly-Cys-Cys-His-Leu-Leu-Ala-Cys-Arg-Phe-Gly-Cys-Ser-Xaa3-Cys-Cys-Xaa4-{circumflexover ( )} (SEQ ID NO:109) Name:     Gm3.3 Species:  gloriamarisCloned:   Yes DNA Sequence:GAGACGACAAGGAACAGTCAACCCCACAGCCACGCCAAGAGCAGACAGCCACAGC (SEQ ID NO:110)TACGTGAAGAAGGGTGGAGAGAGGTTCGTGATGTTGAAAATGGGAGTGGTGCTATTCATCTTCCTGGTACTGTTTCCCCTGGCAACGCTCCAGCTGGATGCAGATCAACCTGTAGAACGATATGCGGAGAACAAACAGCTCCTCAACCCAGATGAAAGGAGGGAAATCATATTGCATGCTCTGGGGACGCGATGCTGTTCTTGGGATGTGTGCGACCACCCGAGTTGTACTTGCTGCGGCGGTTAGCGCCGAACATCCATGGCGCTGTGCTGGGCGGTTTTATCCAACAACGACAGCGTTTGTTGATTTCATGTATCATTGCGCCCACGTCTCTTGTCTAAGAATGACGAACATGATTGCACTCTGGTTCAGATTTCGTGTTCTTTTCTGACAATAAATGACAAAACTCCAAAAAA Translation:MLKMGVVLFIFLVLFPLATLQLDADQPVERYAENKQLLNPDERREIILHALGTRCCSWD (SEQ IDNO:111) VCDHPSCTCCGG Toxin Sequence:Cys-Cys-Ser-Xaa4-Asp-Val-Cys-Asp-His-Xaa3-Ser-Cys-Thr-Cys-Cys-Gly-# (SEQID NO:112) Name:     La3.1 Species:  laterculatus Cloned:   Yes DNASequence: CGACCTCAAGAAGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGA (SEQID NO:113) CCATCTGTCTGCTTCTGTTTCCCCTTACTGCTCTTCCGATGGATGGAGATCAACCTGCAGACCGACCTGCAGAGCGTATGCAGGACGTTTCATCTGAACAGCATCCCTTGTATGATCCCGTCAAACGGTGTTGCGACTGGCCATGCAGCGGATGCATCCCTTGTTGCTAATAGTAACAACGTGTTGATAACCAACTTTCTTACCACGACTACGTCAAGTGTCTAATGAATAAGTAAAATGATTGCAGT Translation:MMSKLGVLLTICLLLFPLTALPMDGDQPADRPAERMQDVSSEQHPLYDPVKRCCDWPC (SEQ IDNO:114) SGCIPCC Toxin Sequence:Cys-Cys-Asp-Xaa4-Xaa3-Cys-Ser-Gly-Cys-Ile-Xaa3-Cys-Cys-{circumflex over( )} (SEQ ID NO:115) Name:     La3.2 Species:  laterculatusCloned:   Yes DNA Sequence:CGACCTCAAGAAGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGA (SEQ ID NO:116)CCATCTGTCTGCTTCTGTTTCCCCTTACTGCTCTGGATGGAGATCAACCTGCAGACCGACTTGCAGAGCGTATGCAGGACGACATTTCATCTGAGCAGCATCCCTTTGAAAAGAGACGAGACTGTTGCACACCTCCGAAGAAATGCAGAGACCGACAATGCAAACCTGCACGTTGTTGCGGAGGATAACGTGTTGATGACCAACTTTGTTATCACGGCTACGTCAAGTGTCTAGTGAATAAGTAAAACGATTGCAGT Translation:MMSKLGVLLTICLLLFPLTALDGDQPADRLAERMQDDISSEQHPFEKRRDCCTPPKKCR (SEQ IDNO:117) DRQCKPARCCGG Toxin Sequence:Arg-Asp-Cys-Cys-Thr-Xaa3-Xaa3-Lys-Lys-Cys-Arg-Asp-Arg-Gln-Cys-Lys-Xaa3-Ala-Arg-Cys-(SEQ ID NO:118) Cys-Gly-# Name:     La3.3 Species:  laterculatusCloned:   Yes DNA Sequence:GGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGC (SEQ IDNO:119) TTCTGTTTCCCCTTACTGCTCTTCCGATGGATGGAGATCAACTTGCACGCCGATCTGCAGAGCGTATGCAGGACAACATTTCATCTGAGCAGCATCACCTCTTTGAAAAGAGACGACCACCATGTTGCACCTATGACGGGAGTTGCCTAAAAGAATCATGCATGCGTAAAGCTTGTTGCGGATGATAACGTGTTGATGACCAACTTTGTTATCACGGCTACTCAAGTGTCTAATGAATAAGTAAAATGATTGCAGTA Translation:MMSKLGVLLTICLLLFPLTALPMDGDQLARRSAERMQDNISSEQHHLFEKRRPPCCTYD (SEQ IDNO:120) GSCLKESCMRKACCG Toxin Sequence:Arg-Xaa3-Xaa3-Cys-Cys-Thr-Xaa5-Asp-Gly-Ser-Cys-Leu-Lys-Xaa1-Ser-Cys-Met-Arg-Lys-(SEQ ID NO:121) Ala-Cys-Cys-# Name:     La3.3A Species:  laterculatusCloned:   Yes DNA Sequence:GGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCACCTGTCTGC (SEQ IDNO:122) TTCTGTTTCCCCTTACTGCTCTTCCGATGGATGGAGATCAACTTGCACGCCGACCTGCAGAGCGTATGCAGGACAACATTTCATCTGAGCAGCATCCCTTCTTTGAAAGGAGACGACCACCATGTTGCACCTATGACGGGAGTTGCCTAAAAGAATCATGCAAGCGTAAAGCTTGTTGCGGATAATAACGTGTTGATGACCAACTTTGTTATCACGGCTACTCAAGTGTCTAATGAATAAGTAAAATGATTGCAGTA Translation:MMSKLGVLLTTCLLLFPLTALPMDGDQLARRPAERMQDNISSEQHPFFERRRPPCCTYD (SEQ IDNO:123) GSCLKESCKRKACCG Toxin Sequence:Arg-Xaa3-Xaa3-Cys-Cys-Thr-Xaa5-Asp-Gly-Ser-Cys-Leu-Lys-Xaa1-Ser-Cys-Lys-Arg-Lys-Ala-(SEQ ID NO:124) Cys-Cys-# Name:     Lp3.1 Species:  leopardusCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCGTCTGTCTGCTTCTGTTTCCCC (SEQ IDNO:125) TTACTGCTCTTCGGCTGGTTGGAGATCAACCTGCAGAGCGACCTGCAAAGCGTACGCAGGACGACATTCCAGATGGACAGCATCCGTTAAATGATAGGCAGATAAACTGTTGCCCGTGGCCATGCCCTAGTACATGCCGCCATCAATGCTGCCATTAATGATAACGTGTTGATGACCAACTTTCTCGAG Translation:GSMMSKLGVLLTVCLLLFPLTALRLVGDQPAERPAKRTQDDIPDGQHPLNDRQINCCPW (SEQ IDNO:126) PCPSTCRHQCCH Toxin Sequence:Xaa2-Ile-Asn-Cys-Cys-Xaa3-Xaa4-Xaa3-Cys-Xaa3-Ser-Thr-Cys-Arg-His-Gln-Cys-Cys-His-{circumflexover ( )} (SEQ ID NO:127) Name:     Lv3.1 Species:  lividusCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCGTCTGTCTGCTTCTGTTTCCCC (SEQ IDNO:128) TTACTGCTCTTCGGCTGGTTAGAGATCAACCTGCAGAGCGACCTGCAAAGCGTACGCAGGACGACATTCCAAATGGACAGGATCCGTTAATTGATAGGCAGATAAATTGTTGCCCTTGGCCATGCCCTGATTCATGCCACTATCAATGCTGCCACTGATAACGTGTTGATGACCAACTTTCTCGAG Translation:GSMMSKLGVLLTVCLLLFPLTALRLVRDQPAERPAKRTQDDIPNGQDPLIDRQINCCPWP (SEQ IDNO:129) CPDSCHYQCCH Toxin Sequence:Xaa2-Ile-Asn-Cys-Cys-Xaa3-Xaa4-Xaa3-Cys-Xaa3-Asp-Ser-Cys-His-Xaa5-Gln-Cys-Cys-His-{circumflexover ( )} (SEQ ID NO:130) Name:     L3.1 Species:  lynceus Cloned:   YesDNA Sequence: AAGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTG(SEQ ID NO:131)CTTCTGTTTCCCCTTACTGCTCTTCCGATGGATGGAGATCAATCTGCAGACCGACTTGCAGAGCGTATGCAGGACAACATTTCATCTGAGCAGCATCCCTTCTTTGAAAAGAGAGGACGAGACTGTTGCACACCTCCGAGGAAATGCAGAGACCGAGCCTGCAAACCTCAACGTTGTTGCGGAGGATAAGCTGTTGATGACCAACTTTGTTATACGGC Translation:MMSKLGVLLTICLLLFPLTALPMDGDQSADRLAERMQDNISSEQHPFFEKRGRDCCTPP (SEQ IDNO:132) RKCRDRACKPQRCCGG Toxin Sequence:Gly-Arg-Asp-Cys-Cys-Thr-Xaa3-Xaa3-Arg-Lys-Cys-Arg-Asp-Arg-Ala-Cys-Lys-Xaa3-Gln-Arg-(SEQ ID NO:133) Cys-Cys-Gly-# Name:     M3.1 Species:  magusCloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ IDNO:134) TCTGCTTCTGTTTCCCCTTACTGCTCTTCCGATGGATGGAGATGAACCTGCAAACCGACCTGTCGAGCGTATGCAGGACAACATTTCATCTGAGCAGTATCCCTTGTTTGAGAAGAGACGAGATTGTTGCACTCCGCCGAAGAAATGCAAAGACCGACAATGCAAACCCCAGAGATGTTGCGCTGGACGATAACGTGTTGATGACCAACTTTATCACGGCTACGTCAAGTGTTTAGTGAATAAGTAAAATGATTGCAGTCTTGCTCAGATTTGCTTTTGTGTTTTGGTCTAAAGATCAATGACCAAACCGTTGTTTTGATGCGGATTGTCATATATTTCTCGATTCCAATCCAACACTAGATGATTTAATCACGATAGATTAATTTTCTATCAATGCCTTGATTTTTCGTCTGTCATATCAGTTTTGTTTATATTTATTTTTTCGTCACTGTCTACACAAACGCATGCATGCACGCATGCACGCACACACGCACGCACGCTCGCACAAACATGCGCGCGCACGCACACACACACACACACACACAAACACACACACGAAGCAATCACACAATTAGTTGACATTATTTATTTATTCATTGATGTATTTGTTATTCGTTTGCTTGTTTTTAGAATAGTTTGAGGCCGTCTTTTTGGATTTATTTGAACTGCTTTATTGTATACGAGTACTTCGTGCGGGGAAACACTGCTGAAAATAAAACAAACACTGACGTAGCAAAAAAA AAAAATranslation: MMSKLGVLLTICLLLFPLTALPMDGDEPANRPVERMQDNISSEQYPLFEKRRDCCTPPK(SEQ ID NO:135) KCKDRQCKPQRCCAGR Toxin Sequence:Arg-Asp-Cys-Cys-Thr-Xaa3-Xaa3-Lys-Lys-Cys-Lys-Asp-Arg-Gln-Cys-Lys-Xaa3-Gln-Arg-Cys-(SEQ ID NO:136) Cys-Ala-# Name:     M3.2 Species:  magus Cloned:   YesDNA Sequence: CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG(SEQ ID NO:137)TCTGCTTCTGTTTCCCCTTACTGCTCTTCCAATGGATGGAGATCAACCTGCAGACCAACCTGCAGATCGTATGCAGGACGACATTTCATCTGAGCAGTATCCCTTGTTTGATATGAGAAAAAGGTGTTGCGGCCCCGGCGGTTCATGCCCCGTATATTTCAGAGACAATTTTATTTGTGGTTGTTGTTAAATGACAACGTGTCGATGACCAACTTCATTATCACGACTACGCCAAGTGTCTAATGAATAAATAAAATGATTGCAGTCTCGCTCAGATTTGCTTTTGTATTTTGGTCTAAAGATCAATGACCAAACCGTTGTTTTGGTGTGGATTTTCATATATTTCTCGAGTCCTATCCAACACTAGATGATTTAATCACGATAGATCTGATTTTTTTATCAAAGGCTTGGTTTTTCGTCTGTCACATCAGTTTTGTTTATATTTAATTTTTCGTCACTGATTACACACACGCATGAACGCACAGAGTACTAACACATACACACACACACACACACACACACACACACACACACACACACACACACACACACACACGCGCGCGCGCGGCGCCATCTAGTAGCGCCGCGACGACACACAC Translation:MMSKLGVLLTICLLLFPLTALPMDGDQPADQPADRMQDDISSEQYPLFDMRKRCCGPG (SEQ IDNO:138) GSCPVYFRDNFICGCC Toxin Sequence:Cys-Cys-Gly-Xaa3-Gly-Gly-Ser-Cys-Xaa3-Val-Xaa5-Phe-Arg-Asp-Asn-Phe-Ile-Cys-Gly-Cys-(SEQ ID NO:139) Cys-{circumflex over ( )} Name:     M3.3 Species:  magusCloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ IDNO:140) TTTGCTTCTGTTTCCCCTTACTGCTCTTCCGAGGGATGGAGATCAATCTGTAGACCGACCTGCAGAGCGTATGCAGGACGACATTTCATCTGAGCTGCATCCCTTGTCAATCAGAAAAAGAATGTGTTGCGGCGAGAGTGCGCCATGCCCCAGCTATTTCAGAAACAGTCAGATTTGTCATTGTTGTTAAATGACAACGTGTCGATGACCACCTTCGTTATCACGACTAATGATAAGTAAAATGATTGCAGTCTCGCTCAGATTTGCTTTTGTATTTTGGTCTAAAGATCAATGACCAAACCGTTGTTTTGATGTGGATTTTCATATATTTCTCGAGTCCTATCCAACACTAGATGATTTAATCACGATAGATCTGATTTTTTTATCAAAGCCTTGGTTTTTCGTCTGTCACATCAGTTTTGTTTATATTTAATTTTTCGTCACTGATTACACACACGCATGAACGCACAGACGTACTAACACATACACACACACACACACACACACACACACACACACACACACACACACACACAC Translation:MMSKLGVLLTICLLLFPLTALPRDGDQSVDRPAERMQDDISSELHPLSIRKRMCCGESAP (SEQ IDNO:141) CPSYFRNSQICHCC Toxin Sequence:Met-Cys-Cys-Gly-Xaa1-Ser-Ala-Xaa3-Cys-Xaa3-Ser-Xaa5-Phe-Arg-Asn-Ser-Gln-Ile-Cys-His-(SEQ ID NO:142) Cys-Cys-{circumflex over ( )} Name:     M3.4Species:  magus Cloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ IDNO:143) TCTGCTTCTGTTTCCCCTTACTGCTCTTCCAATGGATGGAGATCAACCTGCAGACCAACCTGCAGATCGTATGCAGGACGACATTTCATCTGAGCAGTATCCCTTGTTTGATAAGAGACAAAAGTGTTGCGGCCCCGGCGGTTCATGCCCCGTATATTTCACAGACAATTTTATTTGTGGTTGTTGTTAAATGACAACGTGTCGATGACCAACTTCATTATCACGACTACGCCAAGTGTCTAATGAATAAATAAAATGATTGCAGTCTCGCTCAGATTTGCTTTTGTATTTGGTCTAAAGATCAATGACCAAACCGTTGTTTTGGTGCTGGATTTTCATATATTTCTCGATTCCTATCCAACACTAGATGATTTAATCACGATAGATCTGATTTTTTTATCAATGCCTTAATTTTTTGCTCTGTCATATCAGTTTTGTTTATAT Translation:MMSKLGVLLTICLLLFPLTALPMDGDQPADQPADRMQDDISSEQYPLFDKRQKCCGPGG (SEQ IDNO:144) SCPVYFTDNFICGCC Toxin Sequence:Xaa2-Lys-Cys-Cys-Gly-Xaa3-Gly-Gly-Ser-Cys-Xaa3-Val-Xaa5-Phe-Thr-Asp-Asn-Phe-Ile-Cys-(SEQ ID NO:145) Gly-Cys-Cys-{circumflex over ( )} Name:     M3.5Species:  magus Cloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ IDNO:146) TCTGCTTCTGTTTCCCCTTACTGCTCTTCCAATGGATGGAGATCAACCTGCAGACCAACCTGCAGATCGTATGCAGGACGACATTTCATCTGAGCAGTATCCCTTGTTTGATAAGAGACAAAAGTGTTGCGGCCCCGGCGGTTCATGCCCCGTATATTTCAGAGACAATTTTATTTGTGGTTGTTGTTAAATGACAACGTGTCGATGACCATCTTCATTATCACGACTACGCCAAGTGTCTAATGAATAAATAAAATGATTGCAGTCTCGCTCAGATTTGCTTTTGTATTTTGGTCTAAAGATCAATGACCAAACCGTTGTTTTGGTGTGGATTTTCATATATTTCTCGATTCCTATCCAACACTAGATGATTTAATCACGATAGATCTGATTTTTT Translation:MMSKLGVLLTICLLLFPLTALPMDGDQPADQPADRMQDDISSEQYPLFDKRQKCCGPGG (SEQ IDNO:147) SCPVYFRDNFICGCC Toxin Sequence:Xaa2-Lys-Cys-Cys-Gly-Xaa3-Gly-Gly-Ser-Cys-Xaa3-Val-Xaa5-Phe-Arg-Asp-Asn-Phe-Ile-Cys-(SEQ ID NO:148) Gly-Cys-Cys-{circumflex over ( )} Name:     U001Species:  magus Isolated: No Toxin Sequence:Xaa2-Lys-Cys-Cys-Ser-Gly-Gly-Ser-Cys-Xaa3-Leu-Xaa5-Phe-Arg-Asp-Arg-Leu-Ile-Cys-Xaa3-(SEQ ID NO:149) Cys-Cys-{circumflex over ( )} Name:     Comatose/DeathSpecies:  marmoreus Isolated: Yes Toxin Sequence:Ser-Lys-Gln-Cys-Cys-His-Leu-Ala-Ala-Cys-Arg-Phe-Gly-Cys-Thr-Xaa3-Cys-Cys-Asn-{circumflexover ( )} (SEQ ID NO:150) Name:     Mr3.1 Species:  marmoreusCloned:   Yes DNA Sequence:CAAGAAGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ IDNO:151) TCTGCTTCTGTTTCCCGTTACTGCTCTTCCGATGGATGGTGATCAACCTGCAGACCGACTTGTAGAGCGTATGCAGGACAACATTTCATCTGAGCAGCATCCCTTCTTTGAAAAGAGAAGAGGAGGCTGTTGCACACCTCCGAGGAAATGCAAAGACCGAGCCTGCAAACCTGCACGTTGCTGCGGCCCAGGATAACGTGTTGATGACCAACTTTGTTATCACGGCTACGTCAAGTGTCTAGTGAATAAGTAAAACGATTGCAG Translation:MMSKLGVLLTICLLLFPVTALPMDGDQPADRLVERMQDNISSEQHPFFEKRRGGCCTPP (SEQ IDNO:152) RKCKDRACKPARCCGPG Toxin Sequence:Arg-Gly-Gly-Cys-Cys-Thr-Xaa3-Xaa3-Arg-Lys-Cys-Lys-Asp-Arg-Ala-Cys-Lys-Xaa3-Ala-Arg-(SEQ ID NO:153) Cys-Cys-Gly-Xaa3-# Name:     Mr3.2 Species:  marmoreusCloned:   Yes DNA Sequence:GAGCTCGGTACCCCGACCTCAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTG (SEQ ID NO:154)GGAATCTTGTTGACCATCTGTCTACTTCTATTTCCCCTTACTGCTGTTCCGCTGGATGGAGATCAACCTGCAGACCGACCTGCAGAGCGTATGCAGGACGACATTTCATCTGAACATCATCCCTTTTTTGATCCCGTCAAACGGTGTTGCAGGTTATCATGCGGCCTGGGATGCCACCCTTGTTGTGGATGACCAGCTTTGTTATCGCGGCCTCATCAAGTGTCTAAT GAATAAGTAAAATranslation:MMSKLGILLTICLLLFPLTAVPLDGDQPADRPAERMQDDISSEHHPFFDPVKRCCRLSCG (SEQ IDNO:155) LGCHPCCG Toxin Sequence:Cys-Cys-Arg-Leu-Ser-Cys-Gly-Leu-Gly-Cys-His-Xaa3-Cys-Cys-# (SEQ IDNO:156) Name:     Mr3.3 Species:  marmoreus Cloned:   Yes DNA Sequence:GGCCTACACCAAGCTTGCATGCCTGCAGGTCGACTCTAGAGGATCCCCGATCGATA (SEQ ID NO:157)GCAGTTCATGATGTCTAGACTGGGAGTCTTGTTGACCATCTGTCTACTTCTGTTTCCCCTTACTGCTGTTCCGCTGGATGGAGATCAACCTGCGGACCGACCTGCAGAGCGCCTGCAGGACGACATTTCATCTGAACATCATCCCCATTTTGATTCCGGCAGAGAGTGTTGCGGTTCGTTCGCATGCCGCTTTGGATGCGTGCCTTGTTGTGTATGACCAGCTTTGTTATCACGGCCTCATCGAGTGTCTAATGAATAAGTAAAACGATTGCAGTAGGCGGGTACC GAGCTCGAATTCCTranslation:MMSRLGVLLTICLLLFPLTAVPLDGDQPADRPAERLQDDISSEHHPHFDSGRECCGSFAC (SEQ IDNO:158) RFGCVPCCV Toxin Sequence:Xaa1-Cys-Cys-Gly-Ser-Phe-Ala-Cys-Arg-Phe-Gly-Cys-Val-Xaa3-Cys-Cys-Val-{circumflexover ( )} (SEQ ID NO:159) Name:     Mr3.4 Species:  marmoreusCloned:   Yes DNA Sequence:CGACCTCAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGA (SEQ ID NO:160)CCATCTGTCTACTTCTATTTCCCCTTACTGCTGTTCCGCTGGATGGAGACCAACCTGCAGACCGACCTGCAGAGCGTATGCAGGACGACATTTCATCTGAACGTCATCCTTTTTTTGATCGCAGCAAACAGTGTTGCCATCTGCCGGCATGCCGCTTCGGATGTACGCCTTGTTGTTGGTGATCAGCTTTGTTATCGCGTCCTCATCAAGTGTCTAATGAATAAGTAAA ATGATTGCAGTranslation:MMSKLGVLLTICLLLFPLTAVPLDGDQPADRPAERMQDDISSERHPFFDRSKQCCHLPAC (SEQ IDNO:161) RFGCTPCCW Toxin Sequence:Ser-Lys-Gln-Cys-Cys-His-Leu-Xaa3-Ala-Cys-Arg-Phe-Gly-Cys-Thr-Xaa3-Cys-Cys-Xaa4-{circumflexover ( )} (SEQ ID NO:162) Name:     Mr3.5 Species:  marmoreusCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGCTTCTGTTTCCCC (SEQ IDNO:163) TTACTGCTCTTCCGCTGGATGGAGATCAACCTGCAGACCAACGTGCAGAGCGTACGCAGGCCGAGAAGCATTCCTTGCCTGATCCGAGAATGGGCTGTTGCCCGTTTCCATGCAAAACCAGTTGCACTACTTTGTGTTGCGGGTGATGATAACGTGTTGATGACCAACTT TCTCGAGTranslation: GSMMSKLGVLLTICLLLFPLTALPLDGDQPADQRAERTQAEKHSLPDPRMGCCPFPCKT(SEQ ID NO:164) SCTTLCCG Toxin Sequence:Met-Gly-Cys-Cys-Xaa3-Phe-Xaa3-Cys-Lys-Thr-Ser-Cys-Thr-Thr-Leu-Cys-Cys-#(SEQ ID NO:165) Name:     U014 Species:  marmoreus Isolated: Yes ToxinSequence:Cys-Cys-His-Xaa4-Asn-Xaa4-Cys-Asp-His-Leu-Cys-Ser-Cys-Cys-Gly-Ser-{circumflexover ( )} (SEQ ID NO:166) Name:     U017 Species:  marmoreusCloned:   Yes DNA Sequence:GCCAAGCTTGCATGCCTGCAGGATGACTCTAGAGGATCCCCACCTCAAGAGGGATC (SEQ ID NO:167)GATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTACTTCTGTTTGCCCTTACTGCTGTTCCGCTGGATGGAGATCAACCTGCAGACCGACCTGCAGAACGTATGCAGGACGACATTTCATCTGAACGTCATCCCATGTTTGATGCCGTCAGAGATTGTTGCCCGTTGCCGGCATGCCCCTTTGGATGCAACCCTTGTTGTGGATGACCAGCTTTGTTATCGGGACCTCATCAAGTGTCTAATGAATAAGTAAAAAACGATTCGAGTGGGTACCGAGCTCGAATTCC Translation:MMSKLGVLLTICLLLFALTAVPLDGDQPADRPAERMQDDISSERHPMFDAVRDCCPLPA (SEQ IDNO:168) CPFGCNPCCG Toxin Sequence:Asp-Cys-Cys-Xaa3-Leu-Xaa3-Ala-Cys-Xaa3-Phe-Gly-Cys-Asn-Xaa3-Cys-Cys-#(SEQ ID NO:169) Name:     U019 Species:  marmoreus Isolated: Yes ToxinSequence:Cys-Cys-Ala-Xaa3-Ser-Ala-Cys-Arg-Leu-Gly-Cys-Arg-Xaa3-Cys-Cys-Arg-{circumflexover ( )} (SEQ ID NO:170) Name:     U020 Species:  marmoreus Isolated:Yes Toxin Sequence:Cys-Cys-Ala-Xaa3-Ser-Ala-Cys-Arg-Leu-Gly-Cys-Arg-Xaa3-Cys-Cys-Arg-{circumflexover ( )} (SEQ ID NO:171) Name:     U022 Species:  marmoreus Isolated:Yes Toxin Sequence:Cys-Cys-Ala-Xaa3-Ser-Ala-Cys-Arg-Leu-Gly-Cys-Arg-Xaa3-Cys-Cys-Arg-{circumflexover ( )} (SEQ ID NO:172) Name:     U024 Species:  marmoreus Isolated:Yes Toxin Sequence:Gly-Cys-Cys-Gly-Ser-Phe-Ala-Cys-Arg-Phe-Gly-Cys-Val-Xaa3-Cys-Cys-Val-{circumflexover ( )} (SEQ ID NO:173) Name:     Nb3.1 Species:  nobilisCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTACTTCTGTTTCCCC (SEQ IDNO:174) TTACTGCTCTTCCGCTGGATGAAGATCAACCGGTACACCGACCTGCAGAGCGTATGCAGGACATTTCATCTGATCAACATCTCTTCTTTGATCTCATCAAACGGTGCTGCGAGTTGCCATGCGGGCCAGGCTTTTGCGTCCCTTGTTGCTGACATCAATAACGTGTTGATGACCAACTTTCTCGAG Translation:GSMMSKLGVLLTICLLLFPLTALPLDEDQPVHRPAERMQDISSDQHLFFDLIKRCCELPCG (SEQ IDNO:175) PGFCVPCC Toxin Sequence:Cys-Cys-Xaa1-Leu-Xaa3-Cys-Gly-Xaa3-Gly-Phe-Cys-Val-Xaa3-Cys-Cys-{circumflexover ( )} (SEQ ID NO:176) Name:     Nb3.2 Species:  nobilisCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTACTTCTGTTTCCCC (SEQ IDNO:177) TTACTGCTTTTCCGATGGATGGAGATCAACCTGCAGACCAACCTGCAGATCGTATGCAGGACGACATTTCATCTGAGCAGTATCCCTTGTTTGATAAGAGACAAAAGTGTTGCACTGGGAAGAAGGGGTCATGCTCCGGCAAAGCATGCAAAAATCTCAAATGTTGCTCTGGACGATAACGTGTTGATGACCAACTTTCTCGAG Translation:GSMMSKLGVLLTICLLLFPLTAFPMDGDQPADQPADRMQDDISSEQYPLFDKRQKCCTG (SEQ IDNO:178) KKGSCSGKACKNLKCCSGR Toxin Sequence:Xaa2-Lys-Cys-Cys-Thr-Gly-Lys-Lys-Gly-Ser-Cys-Ser-Gly-Lys-Ala-Cys-Lys-Asn-Leu-Lys-Cys-(SEQ ID NO:179) Cys-Ser-# Name:     Pu3.1 Species:  pulicariusCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTTTTGTTGACCATCTGTCTGCTTCTGTTTCCCC (SEQ IDNO:180) TTACTGCTGTTCCGCTGGATGGAGATCAACCTGCAGACCGACCTGCAGAGCGTATGCAGGACATTGCAACTGAACAGCATCCCTTCTTTGATCCCGTCAAACGGTGTTGCAACAGCTGTTACATGGGATGCATCCCTTGTTGCTTCTAGTAATAACGTGTTGATGACCAAC TTTCTCGAGTranslation: GSMMSKLGVLLTICLLLFPLTAVPLDGDQPADRPAERMQDIATEQHPFFDPVKRCCNSC(SEQ ID NO:181) YMGCIPCCF Toxin Sequence:Cys-Cys-Asn-Ser-Cys-Xaa5-Met-Gly-Cys-Ile-Xaa3-Cys-Cys-Phe-{circumflexover ( )} (SEQ ID NO:182) Name:     Qc3.1 Species:  quercinusCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGCTTCTGTTTCCCC (SEQ IDNO:183) TTACAGCTCTTCAGCTGGATGGAGATCAACCTGCAGACCGACCTGCAGAGCGTACGCAGGACATTGCATCTGAACAGTATCGAAAGTTTGATCAGAGACAGAGGTGTTGCCAGTGGCCATGCCCCGGTAGTTGCAGATGCTGCCGTACTGGTTAACGTGTTGATGACCA ACTTTCTCGAGTranslation: GSMMSKLGVLLTICLLLFPLTALQLDGDQPADRPAERTQDIASEQYRKFDQRQRCCQWP(SEQ ID NO:184) CPGSCRCCRTG Toxin Sequence:Xaa2-Arg-Cys-Cys-Gln-Xaa4-Xaa3-Cys-Xaa3-Gly-Ser-Cys-Arg-Cys-Cys-Arg-Thr-#(SEQ ID NO:185) Name:     QcIIIA Species:  quercinus Isolated: Yes ToxinSequence:Cys-Cys-Ser-Gln-Asp-Cys-Leu-Val-Cys-Ile-Xaa3-Cys-Cys-Xaa3-Asn-# (SEQ IDNO:186) Name:     QcIIIB Species:  quercinus Isolated: Yes ToxinSequence:Cys-Cys-Ser-Arg-His-Cys-Xaa4-Val-Cys-Ile-Xaa3-Cys-Cys-Xaa3-Asn-? (SEQ IDNO:187) Name:     R3.1 Species:  radiatus Isolated: Yes Cloned:   YesDNA Sequence: TCAAGAAGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCT(SEQ ID NO:188)GTCTGCTTCTGTTTCCCCTTACTGCTCTTCCGATGGATGGAGATCAACCTGTAGACCGACTTGCAGAGCGTATGCAGGACAACATTTCATCTGAGCAGCATACCTTCTTTGAAAAGAGACTACCATCGTGTTGCTCCCTTAACTTGCGGCTTTGCCCAGTACCAGCATGCAAACGTAACCCTTGTTGCACAGGATAACGTGTTGATGACCAACTTTGTTATCACGGCTACGTCAAGTGTCTAGTGAATAAGTAAAACGATTGCAGT Translation:MMSKLGVLLTICLLLFPLTALPMDGDQPVDRLAERMQDNISSEQHTFFEKRLPSCCSLNL (SEQ IDNO:189) RLCPVPACKRNPCCTG Toxin Sequence:Leu-Xaa3-Ser-Cys-Cys-Ser-Leu-Asn-Leu-Arg-Leu-Cys-Xaa3-Val-Xaa3-Ala-Cys-Lys-Arg-Asn-(SEQ ID NO:190) Xaa3-Cys-Cys-Thr-# Name:     R3.2 Species:  radiatusCloned:   Yes DNA Sequence:AGGTCGACTCTAGAGGATCCCCAAGGATCGATAGCAGTTCATGATGTCTAAACTGG (SEQ ID NO:191)GAGTCTTGTTGACCATCTGTCTGCTTCTGTTTCCCCTTACTGCTCTTCCGATGGATGGAGATCAACCTGCAGACCGACTTGCAGAGCGTATGCAGGACGACATTTCATCTGAGCAGCATCCCTTCTTTAAAAAGAGACAACAAAGATGTTGCACCGTTAAGAGGATTTGTCCAGTACCAGCATGCAGAAGTAAACCTTGTTGCAAATCATAACGTATTGATGACCAACTTTGTTATCACGGCTACGTCAAGTGTCTAGTGAATAAGTAAAATGATTGCAG Translation:MMSKLGVLLTICLLLFPLTALPMDGDQPADRLAERMQDDISSEQHPFFKKRQQRCCTVK (SEQ IDNO:192) RICPVPACRSKPCCKS Toxin Sequence:Xaa2-Gln-Arg-Cys-Cys-Thr-Val-Lys-Arg-Ile-Cys-Xaa3-Val-Xaa3-Ala-Cys-Arg-Ser-Lys-Xaa3-(SEQ ID NO:193) Cys-Cys-Lys-Ser-{circumflex over ( )} Name:     R3.3Species:  radiatus Cloned:   Yes DNA Sequence:ACCTCAAGAAGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACC (SEQ ID NO:194)ATCTGTCTGCTTCTGTTTCCCGTTACTGCTCTTCCGATGGATGGTGATCAACCTGCAGACCGACTTGTAGAGCGTATGCAGGACAACATTTCATCTGAGCAGCATCCCTTCTTTGAAAAGAGAAGAGGAGGCTGTTGCACACCTCCGAGGAAATGCAAAGACCGAGCCTGCAAACCTGCACGTTGCTGCGGCCCAGGATAACGTGTTGATGACCAACTTTGTTATCACGGCTACGTCAAGTGTCTAGTGAATAAGTAAAACGATTGCAGT Translation:MMSKLGVLLTICLLLFPVTALPMDGDQPADRLVERMQDNISSEQHPFFEKRRGGCCTPP (SEQ IDNO:195) RKCKDRACKPARCCGPG Toxin Sequence:Arg-Gly-Gly-Cys-Cys-Thr-Xaa3-Xaa3-Arg-Lys-Cys-Lys-Asp-Arg-Ala-Cys-Lys-Xaa3-Ala-Arg-(SEQ ID NO:196) Cys-Cys-Gly-Xaa3-# Name:     Ra3.1 Species:  rattusCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGGTGACCATCTGCCTGCTTCTGTTCCCT (SEQ IDNO:197) CTTGCTGCTTTTCCACTGGATGGAGATCAACCTGCAGACCACCCTGCAAAGCGTACGCAAGATGACAGTTCAGCTGCCCTGATCAATGCCTGGCTTGATGAATCCCAGACTTGCTGCAGTAACTGCGGTGAAGATTGTGATGGTTGTTGCCAGTAACGTGTTGATGACCAA CTTTCTCGAGTranslation: GSMMSKLGVLVTICLLLFPLAAFPLDGDQPADHPAKRTQDDSSAALINAWLDESQTCCS(SEQ ID NO:198) NCGEDCDGCCQ Toxin Sequence:Xaa2-Thr-Cys-Cys-Ser-Asn-Cys-Gly-Xaa1-Asp-Cys-Asp-Gly-Cys-Cys-Gln-{circumflexover ( )} (SEQ ID NO:199) Name:     Sm3.1 Species:  stercusmuscarumCloned:   Yes DNA Sequence:GACCTCAAGAGGGATCGATAGCAGTTCGTGATGTCTAAACTGGGAGTCTTGTTGAC (SEQ ID NO:200)CATCTGTCTGCTTCTGTTTCCTCTTACTGCTCTTCCGATGGATGGAGATCAACCTGCAGACCAACCTGCAGATCGTATGCAGGACGACATTTCATCTGAGCAGTATCCCTTGTTTGATAAGAGACAAAAGTGTTGCACTGGGAAGAAGGGGTCATGCTCCGGCAAAGCATGCAAAAATCTCAAATGTTGCTCTGGACGATAACGTGTTGATGACCAACTTTGTTATCACGGCTACGTCAAGTGTCTAATGAATAAGTAAAACGATTGCAGT Translation:MSKLGVLLTICLLLFPLTALPMDGDQPADQPADRMQDDISSEQYPLFDKRQKCCTGKKG (SEQ IDNO:201) SCSGKACKNLKCCSGR Toxin Sequence:Xaa2-Lys-Cys-Cys-Thr-Gly-Lys-Lys-Gly-Ser-Cys-Ser-Gly-Lys-Ala-Cys-Lys-Asn-Leu-Lys-Cys-(SEQ ID NO:202) Cys-Ser-# Name:     U034 Species:  stercusmuscarumIsolated: Yes Cloned:   Yes DNA Sequence:GATCGATAGCAGTTCGTGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGCTT (SEQ IDNO:203) CTGTTTCCCCTTACTGCTCTTCCGATGGATGGAGATCAACCTGCAGACCAACCTGCAGATCGTATGCAGAACGACATTTCATCTGAGCAGTATCCCTTGTTTGATAAGAGACAAAAGTGTTGCGGCCCCGGCGCGTCATGCCCCAGATATTTCAAAGACAATTTTATTTGTGGTTGTTGTTAAATGACAACGTGTCGATGACCAACTTCGTTATCACGACTTCGCCAAGTGTCTAATGAATAAGTAAAACGATTGCAGT Translation:MSKLGVLLTICLLLFPLTALPMDGDQPADQPADRMQNDISSEQYPLFDKRQKCCGPGAS (SEQ IDNO:204) CPRYFKDNFICGCC Toxin Sequence:Xaa2-Lys-Cys-Cys-Gly-Xaa3-Gly-Ala-Ser-Cys-Xaa3-Arg-Xaa5-Phe-Lys-Asp-Asn-Phe-Ile-Cys-(SEQ ID NO:205) Gly-Cys-Cys-{circumflex over ( )} Name:     S3.1Species:  striatus Cloned:   Yes DNA Sequence:CGACCTTTCAAGAGGGATCGATAGCAGTTCGCGATGTCTAAACTGGGGGTATTGTTG (SEQ IDNO:206) ACCATCTGTCTGCTTCTGTTTCCCCTTACTGCTCTTCCGATGGATGAAGATCAACCTGCAGACCAACTTGAAGATCGTATGCAGGACGACATTTCATCTGAGCAGTATCCCTCGTTTGTTAGGAGACAAAAGTGTTGCGGCGAAGGCTCGTCATGCCCCAAATATTTCAAAAACAATTTTATTTGTGGTTGTTGTTAAATGACAACGTGTCGATGACCAACTTCGTTATCACGACTACGCCAAGTGTCTTGTCTAATGATAATAAAATGATTCC Translation:MSKLGVLLTICLLLFPLTALPMDEDQPADQLEDRMQDDISSEQYPSFVRRQKCCGEGSSC (SEQ IDNO:207) PKYFKNNFICGCC Toxin Sequence:Xaa2-Lys-Cys-Cys-Gly-Xaa1-Gly-Ser-Ser-Cys-Xaa3-Lys-Xaa5-Phe-Lys-Asn-Asn-Phe-Ile-Cys-(SEQ ID NO:208) Gly-Cys-Cys-{circumflex over ( )} Name:     S3.2Species:  striatus Cloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCGTCTGTCTGCTTCTGTTTCCCC (SEQ IDNO:209) TTACTGCTCTTCCGCTGGATGGAGATCAACCTGCAGACCGACCTGCAGAGCGTATGCAGGACGACATTTCATCTGACGAGCATCCCTTGTTTGATAAGAGACAAAACTGTTGCAATGGGGGATGCTCCAGCAAATGGTGCAGAGATCACGCACGTTGTTGCGGTCGATGATAACGTGTTGATGACCAACTTTCTCGAG Translation:GSMMSKLGVLLTVCLLLFPLTALPLDGDQPADRPAERMQDDISSDEHPLFDKRQNCCNG (SEQ IDNO:210) GCSSKWCRDHARCCGR Toxin Sequence:Xaa2-Asn-Cys-Cys-Asn-Gly-Gly-Cys-Ser-Ser-Lys-Xaa4-Cys-Arg-Asp-His-Ala-Arg-Cys-Cys-#(SEQ ID NO:211) Name:     Ts3.1 Species:  tessulatus Cloned:   Yes DNASequence: GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATGTGTCTGCTTCTGTTTCCCC(SEQ ID NO:212) TTACTGCTGTTCCGCTGGATGGAGATCAACCTGCAGACCGACCTGCAGAGCGTAGGCAGGACATTGCAACTGACGATCATCCTTTGTTTGATCCCGTCAAACGGTGCTGCCACAAATGCTATATGGGATGCATCCCTTGTTGCATTTAGTAACGTGTTGATGACCAACTT TCTCGAGTranslation: GSMMSKLGVLLTMCLLLFPLTAVPLDGDQPADRPAERRQDIATDDHPLFDPVKRCCHK(SEQ ID NO:213) CYMGCIPCCI Toxin Sequence:Cys-Cys-His-Lys-Cys-Xaa5-Met-Gly-Cys-Ile-Xaa3-Cys-Cys-Ile-{circumflexover ( )} (SEQ ID NO:214) Name:     Ts3.2 Species:  tessulatusCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTGTGCTTCTGTTTCCCC (SEQ IDNO:215) TTACTGCTGTTCCGCTGGATGGAGATCAACCTGCAGACCAACCTGCAGAGCGTACGCAGAACGAGCAGCATCCCTTGTATGATCAGAAAAGAAAGTGTTGCCGGCCGCCATGCGCCATGAGCTGCGGCATGGCTAGGTGTTGCTATTAATGATAACGTGTTGATGACCA ACTTTCTCGAGTranslation: GSMMSKLGVLLTICVLLFPLTAVPLDGDQPADQPAERTQNEQHPLYDQKRKCCRPPCA(SEQ ID NO:216) MSCGMARCCY Toxin Sequence:Lys-Cys-Cys-Arg-Xaa3-Xaa3-Cys-Ala-Met-Ser-Cys-Gly-Met-Ala-Arg-Cys-Cys-Xaa5-{circumflexover ( )} (SEQ ID NO:217) Name:     Circling Species:  textile Isolated:Yes Cloned:   Yes DNA Sequence:GAGTCAACCCACTGTCACGCCAAGAGCGGACGCCACAGCTAAGGCAAGAAGGATC (SEQ ID NO:218)GATAGCAGTTCATGATGTCTAAACTGGGAGCCTTGTTGACCATCTGTCTACTTCTGTTTTCCCTTACTGCTGTTCCGCTGGATGGAGATCAACATGCAGACCAACCTGCACAGCGTCTGCAGGACCGCATTCCAACTGAAGATCATCCCTTATTTGATCCCAACAAACGGTGTTGCCCGCCGGTGGCATGCAACATGGGATGCAAGCCTTGTTGTGGATGACCAGCTTTGTTATCGCGGTCTCATGAAGTGTCTAATGAATAAGTAAAACGATTGCAGTTTCGTTCAGATTTGCTGTTGTATTTTGGTCTAAAGATTAATGACCAAACTGTTCTTTTGATCCGGATTTTCACGTATTTCTCGATTCCTATTCAACACTAGATAAGTTAATCACGACAGATCTGATTTTCCATCAATGCCTTGCTTTTTGGTCTGTCATATAAATCTTGTTTATATTTAATTTCTCGTCACTTTCAACACGCACACACACACACACACACACGCGCGCGC Translation:MMSKLGALLTICLLLFSLTAVPLDGDQHADQPAQRLQDRIPTEDHPLFDPNKRCCPPVA (SEQ IDNO:219) CNMGCKPCCG Toxin Sequence:Cys-Cys-Xaa3-Xaa3-Val-Ala-Cys-Asn-Met-Gly-Cys-Lys-Xaa3-Cys-Cys-Gly-{circumflexover ( )} (SEQ ID NO:220) Name:     Scratcher I Species:  textileCloned:   Yes DNA Sequence:GGATCCAGACGACAAAGAAGAGTCAACCCACTGCCACGTCAAGAGCAGAGCCCAC (SEQ ID NO:221)AGCTAAGACAAGAAGGATCGATAGCAGTTCATGATGTTTAAACTGGGAGTCTTGTTGACCATCTGTCTCCTTCTGTTTTCCCTTAATGCTGTTCCGTTGGATGGAGATCAACCTGCAGACCAACCTGCAGAGCGTCTGCTGGACGACATTTCATTTGAAAATAATCCCTTTTATGATCCCGCCAAACGGTGTTGCAGGACTTGCTTCGGTTGCACACCTTGTTGTGGATGACCAGCCTCATCAAGTGTCTAACGAATAAGTAAAGCGATTGCAGTCTCGTTCAGATTTACTTTTGTATTCTGGTCTAAAGATTAATGACCAAACTCTTCTTTTGATCCGGATGTACATATATTTCTCGATTCCTATCCAACGCTAGATAAGCTAATCACGACAGATCTGATTTTCTGTCAATGCCTTGCTTTTTGGTCTCTCATATCACTCTTGTTTATATTTAATTTCTCGTCACTATATATATATATACACACACACACACACGGAATTCCGATTGTCCAGTACCGTTCTTGGGATCGAGGTATTGCTGCGATGGCTTATTCTGTACTCTTTTCTTCTGCGCTTGATAGTGATGTCTTCTACTCCCATCTGTGCTACCCCTGGCTTGATCTTTGATAGGCGTGTGCCCTTCACTGGTTATAAACCCCTCTGATCCTACTCTCTGGACGCCTCGGGGGCCCAACCTCCAAATAAAGCGACATCCAATGAAAAAA Translation:MMFKLGVLLTICLLLFSLNAVPLDGDQPADQPAERLLDDISFENNPFYDPAKRCCRTCFG (SEQ IDNO:222) CTPCCG Toxin Sequence:Cys-Cys-Arg-Thr-Cys-Phe-Gly-Cys-Thr-Xaa3-Cys-Cys-# (SEQ ID NO:223)Name:     Tx3.1 Species:  textile Cloned:   Yes DNA Sequence:GGAACAGTCAACCCCACAGCCACGCCAAGAGCAGACAGCCACAGCTACGTGAAGA (SEQ ID NO:224)AGGGTGGAGAGAGGTTCATGATGTTGAAAATGGGAGTGGTGCTATTCATCTTTCTGGTACTGTTTCCCCTGGCAACGCTCCAGCTGGATGCAGATCAACCTGTAGAACGATATGCGGAGAACAAACAGCTCCTCAACCCAGATGAAAGGAGGGAAATCCTATTGCCTGCTCTGAGGAAGTTCTGCTGTGATTCGAATTGGTGCCACATTTCGGATTGTGAGTGCTGCTACGGTTAGCGCCGAACATCCATGGCACTGTGCTGGGCGGTTTCATCCCAACAACGACAGCGTTTGTTGATTTCATGTATCATTGCGCCCACGTCTCTTGTCTAAGAATGACGAACATGATTGCACTCTGGTTCAGATTTCGTGTTCTTTTCTGACAATAAATGACAAAcC TCCTranslation: MMLKMGVVLFIFLVLFPLATLQLDADQPVERYAENKQLLNPDERREILLPALRKFCCDS(SEQ ID NO:225) NWCHISDCECCYG Toxin Sequence:Phe-Cys-Cys-Asp-Ser-Asn-Xaa4-Cys-His-Ile-Ser-Asp-Cys-Xaa1-Cys-Cys-Xaa5-#(SEQ ID NO:226) Name:     U031 Species:  textile Isolated: YesCloned:   Yes DNA Sequence:CAAGGAACAGTCAACCCCACAGCCACGCCAAGAGCAGACAGCCACAGCTACGTGA (SEQ ID NO:227)AGAAGGGTGGAGAGAGGTTCGTGATGTTGAAAATGGGAGTGGTGCTATTCATCTTCCTGGTACTGTTTCCCCTGGCAACGCTCCAGCTGGATGCAGATCAACCTGTAGAACGATATGCGGAGAACAAACAGCTCCTCAGCCCAGATGAAAGGAGGGAAATCATATTGCATGCTCTGGGGACGCGATGCTGTTCTTGGGATGTGTGCGACCACCCGAGTTGTACTTGCTGCGGTTAGCGCCGAACATCCATGGCGCTGTGCTGGGCGGTTTTATCCCAACAACGACAGCGTTTGTTGATTTCATGTATCATTGCGCCCACGTCTCTTGTCTAAGAATGACGAACATGATTGCACTCTGGTTCAGATTTCGTGTTCTTTTCTGACAATAAATGACAAAA CNCCTranslation: MLKMGVVLFIFLVLFPLATLQLDADQPVERYAENKQLLSPDERREIILHALGTRCCSWD(SEQ ID NO:228) VCDHPSCTCCG Toxin Sequence:Cys-Cys-Ser-Xaa4-Asp-Val-Cys-Asp-His-Xaa3-Ser-Cys-Thr-Cys-Cys-# (SEQ IDNO:229) Name:     U032 Species:  textile Isolated: Yes Cloned:   Yes DNASequence: GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGCTTCTGTTTCCCC(SEQ ID NO:230) TTACTGCTCTTCCGCTGGATGGAGATCAACCCGCAGACCAAGCTGCAGAGCGTATGCAGGCCGAGCAGCATCCCTTGTTTGATCAGAAAAGACGGTGCTGCAAGTTTCCATGCCCCGATAGTTGCAGATATTTGTGTTGCGGGTGATGATAACGTGTTGATGACCAACT TTCTCGAGTranslation: GSMMSKLGVLLTICLLLFPLTALPLDGDQPADQAAERMQAEQHPLFDQKRRCCKFPCPD(SEQ ID NO:231) SCRYLCCG Toxin Sequence:Arg-Cys-Cys-Lys-Phe-Xaa3-Cys-Xaa3-Asp-Ser-Cys-Arg-Xaa5-Leu-Cys-Cys-#(SEQ ID NO:232) Name:     T3.1 Species:  tulipa Cloned:   Yes DNASequence: CGACCTCAAGAGGGATCGATAGCAGTTCATGTCTAAACTGGGAGTCTTGTTGACAA (SEQID NO:233) TCTGTCTGCTTCTGTTTCCCCTTACTGCTCTGCCGATGGATGGAGATGAACCTGCAGACCGACCTGCAGAGCGTATGCAGGACAACATTTCATCTGAGCAGCATCCCTTGTTTGAGGAGAGACACGGATGTTGCAAGGGGCCCGAAGGATGCTCCTCCAGAGAATGCAGACCCCAACATTGTTGCGGTCGACGATAACGTGTTGAGGGCCAACTTTGTTATCACGGCTACGTCAAGTGTTTAGTGAATAAGTAAAATGATTGCAG Translation:MSKLGVLLTICLLLFPLTALPMDGDEPADRPAERMQDNISSEQHPLFEERHGCCKGPEGC (SEQ IDNO:234) SSRECRPQHCCGRR Toxin Sequence:His-Gly-Cys-Cys-Lys-Gly-Xaa3-Xaa1-Gly-Cys-Ser-Ser-Arg-Xaa1-Cys-Arg-Xaa3-Gln-His-Cys-(SEQ ID NO:235) Cys-# Name:     Fi3.1 Species:  figulinus Cloned:   YesDNA Sequence: CAAGAAGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGCTGACCATCT(SEQ ID NO:236)GTCTGCTTCTGATTCCCCTTACTGCTCTTTCGCTGGATGGAGATCAACCTGCAGACCGACCTGCAGAGCGTATGCAGGATGGAATTTCATCTGAACAGCATCCCATGTTTGATCCCGTCAGACGGTGTTGCCCGTGGCCATGCAACATAGGATGCGTACCTTGTTGTTGATGACCAGTTTTGTTATCGCGGCCTCATCAAATGTCTAATGAATAAGTAAAACGATTGC AGTTranslation: MMSKLGVLLTICLLLIPLTALSLDGDQPADRPAERMQDGISSEQHPMFDPVRRCCPWPC(SEQ ID NO:237) NIGCVPCC Toxin Sequence:Cys-Cys-Xaa3-Xaa4-Xaa3-Cys-Asn-Ile-Gly-Cys-Val-Xaa3-Cys-Cys-{circumflexover ( )} (SEQ ID NO:238) Name:     Fi3.2 Species:  figulinusCloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTTTAAACTGGGAGTCCTGTTGACCATCTG (SEQ IDNO:239) TATGCTTCTGTTTCCCTTTACTGCTCTTCCGCTGGATGGAGAGCAACCTGCAGACCAACCTGCAGAGCGCATGCAGTATGACATGTTACGTGCAATGAATCCCTGGTTTGATCCCGTCAAAAGGTGCTGCTCGAAGAACTGCGCAGTATGCATCCCTTGTTGCCCGTAACTGACCAGCTTGATTATCGCGGCCAAGGCTCTAATGAATAAGTAAAACGATTGCAGT Translation:MMFKLGVLLTICMLLFPFTALPLDGEQPADQPAERMQYDMLRAMNPWFDPVKRCCSK (SEQ IDNO:240) NCAVCIPCCP Toxin Sequence:Cys-Cys-Ser-Lys-Asn-Cys-Ala-Val-Cys-Ile-Xaa3-Cys-Cys-Xaa3-{circumflexover ( )} (SEQ ID NO:241) Name:     Fi3.3 Species:  figulinusCloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGAGAGTCTTGTTGACCTTATG (SEQ IDNO:242) TCTGCTTCTGTTTCCCCTTACTGCTCTTCCGCTGAATGAAGATCAACCTGCAGAGCGTATGCAGGACGACAATTCATCTGAGCAGCACCCCTTGTATGACCACAAACGAAAGTGTTGCCGGTGGCCATGCCCCGCAAGATGCGGCTCTTGTTGCCTGTAATAACGTGTTGGCCAACTTTGTTATCACGGCCACGTCAAATGTTTAATGAATAAGTAAAACGATTGCAG T Translation:MMSKLRVLLTLCLLLFPLTALPLNEDQPAERMQDDNSSEQHPLYDHKRKCCRWPCPAR (SEQ IDNO:243) CGSCCL Toxin Sequence:Cys-Cys-Arg-Xaa4-Xaa3-Cys-Xaa3-Ala-Arg-Cys-Gly-Ser-Cys-Cys-Leu-{circumflexover ( )} (SEQ ID NO:244) Name:     Fi3.4 Species:  figulinusCloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCTTATG (SEQ IDNO:245) TCTGCTTCTGTTTCCCCTGACTGCTCTTCCGCTGGATGAAGATCAAGCTGCAGACCGACCTGCAGAGCGTATGCAGGGCATGTCATCTGAACAGCATCCCTTCTTTGATCCCGTCAAACGGTGTTGCGAGTTGTCACGCTGCCTTGGATGCGTCCCTTGTTGCACATCTTAATAACGTGTGGATGACCAACTGTGTTATCACGGCCACGTCAAGTGTCTAATGAATAAGTAAAATGATTGCAGT Translation:MMSKLGVLLTLCLLLFPLTALPLDEDQAADRPAERMQGMSSEQHPFFDPVKRCCELSRC (SEQ IDNO:246) LGCVPCCTS Toxin Sequence:Cys-Cys-Xaa1-Leu-Ser-Arg-Cys-Leu-Gly-Cys-Val-Xaa3-Cys-Cys-Thr-Ser-{circumflexover ( )} (SEQ ID NO:247) Name:     Fi3.5 Species:  figulinusCloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCTTATG (SEQ IDNO:248) TCTGCTTCTGTTTCCCCTGACTGCTCTTCCGCTGGATGAAGATCAACCTGCAGACCGACCTGCAGAGCGTATGCAGGGCATGTCATCTGAACAGCATCCCTTCTTTGATCCCGTCAAACGGTGTTGCGAGTTGTCAAAATGCCATGGATGCGTCCCTTGTTGCATACCTTAATAACGTGCGGATGACCAACTGTGTTATCACGGCCACGTCAAGTGTCTAATGAATAAGTAAAATGATTGCAGT Translation:MMSKLGVLLTLCLLLFPLTALPLDEDQPADRPAERMQGMSSEQHPFFDPVKRCCELSKC (SEQ IDNO:249) HGCVPCCIP Toxin Sequence:Cys-Cys-Xaa1-Leu-Ser-Lys-Cys-His-Gly-Cys-Val-Xaa3-Cys-Cys-Ile-Xaa3-{circumflexover ( )} (SEQ ID NO:250) Name:     Qc3.2 Species:  quercinusCloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTCGGAGTCTTGTTGACCATCTG (SEQ IDNO:251) TCTGGTTCTGTTTCCCCTTACAGCTCTTCAGCTGGATGGAGATCAACCTGCAGACCGACCTGCAGAGCGTACGCAGGACATTTCATCTGAACAGTATCGAAAGTTTGATCAGAGACAGAGGTGTTGCCGGTGGCCATGCCCCGGTAGTTGCAGATGCTGCCGTTATCGTTAACGTGTTGGTGACCAGCTTTGTTATCACGACCACGCCAAGTGTCTAACGAATAAGT AAAATGATTGCAGTTranslation: MMSKLGVLLTICLVLFPLTALQLDGDQPADRPAERTQDISSEQYRKFDQRQRCCRWPCP(SEQ ID NO:252) GSCRCCRYR Toxin Sequence:Xaa2-Arg-Cys-Cys-Arg-Xaa4-Xaa3-Cys-Xaa3-Gly-Ser-Cys-Arg-Cys-Cys-Arg-Xaa5-Arg-{circumflexover ( )} (SEQ ID NO:253) Name:     Qc3.3 Species:  quercinusCloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ IDNO:254) TCTGCTTCTGTTTCCCCTTACTGCTCTTCCACTGGATGGAGATCAACCTGCAGATCAATCTGCAGAGCGACCTGCAGAGCGTACGCAGGACGACATTCAGCAGCATCCGTTATATGATCCGAAAAGAAGGTGTTGCCGTTATCCATGCCCCGACAGCTGCCACGGATCTTGCTGCTATAAGTGATAACATGTTGATGGCCAGCTTTGTTATCACGGCCACGTCAAGTGTCTAATGAATAAGTAAAACGATTGCAGT Translation:MMSKLGVLLTICLLLFPLTALPLDGDQPADQSAERPAERTQDDIQQHPLYDPKRRCCRY (SEQ IDNO:255) PCPDSCHGSCCYK Toxin Sequence:Arg-Cys-Cys-Arg-Xaa5-Xaa3-Cys-Xaa3-Asp-Ser-Cys-His-Gly-Ser-Cys-Cys-Xaa5-Lys-{circumflexover ( )} (SEQ ID NO:256) Name:     Wi3.1 Species:  wittigiCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGCTTCTGTTTCCCA (SEQ IDNO:257) TTACTGCTCTTCCGGTGGGTGGAGATCAGCCTGCAGACCGACTTGCAGAGCGTATGCAGGACGACACTTCATCTGAGCAGCATCCCTTTGAAAAGAGACTACCATCATGTTGCGACTTTGAGAGGCTTTGCGTAGTACCAGCATGCATACGTCATCAGTGTTGCACAGGATAACGTGTTGATGACCAACTTTCTCGAG Translation:MMSKLGVLLTICLLLFPITALPVGGDQPADRLAERMQDDTSSEQHPFEKRLPSCCDFERL (SEQ IDNO:258) CVVPACIRHQCCTG Toxin Sequence:Leu-Xaa3-Ser-Cys-Cys-Asp-Phe-Xaa1-Arg-Leu-Cys-Val-Val-Xaa3-Ala-Cys-Ile-Arg-His-Gln-(SEQ ID NO:259) Cys-Cys-Thr-# Name:     bt3a Species:  betulinusIsolated: Yes Toxin Sequence:Cys-Cys-Lys-Gln-Ser-Cys-Thr-Thr-Cys-Met-Xaa3-Cys-Cys-Xaa4-{circumflexover ( )} (SEQ ID NO:260) Name:     T3.2 Species:  tulipa Cloned:   YesDNA Sequence: GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACAATCTGTCTGCTTCTGTTTCCCC(SEQ ID NO:261) TTACTGCTCTGCCGATGGATGGAGATGAACCTGCAGACCGACCTGCAGAGCGTATGCAGGACAACATTTCATCTGAGCAGCATCCCTTGTTTGAGGAGAGACACGGATGTTGCGAGGGGCCGAAGGGATGCTCCTCCAGAGAATGCAGACCCCAACATTGTTGCGGTCGACGATAACGTGTTGATGACCAACTNTCTCGAG Translation:MMSKLGVLLTICLLLFPLTALPMDGDEPADRPAERMQDNISSEQHPLFEERHGCCEGPK (SEQ IDNO:262) GCSSRECRPQHCCGRR Toxin Sequence:His-Gly-Cys-Cys-Xaa1-Gly-Xaa3-Lys-Gly-Cys-Ser-Ser-Arg-Xaa1-Cys-Arg-Xaa3-Gln-His-Cys-(SEQ ID NO:263) Cys-# Name:     A3.5 Species:  aurisiacus Cloned:   YesDNA Sequence: GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTACTTCTGTTTCCCC(SEQ ID NO:264)TTACTGCTTTTCCGATGGATGGAGATCAACCTGCAGACCAACCTGCAGATCGTATGCAGGACGACATTTCATCTGAGCAGTATCCCTTGTTTGATAAGAGACAAAAGTGTTGCACTGGGAGGAAGGGGTCATGCTCCGGCAAAGCATGCAAAAATCTCAAATGTTGCTCTGGACGATAACGTGTTGATGACCAACTTTCTCGAN Translation:MMSKLGVLLTICLLLFPLTAFPMDGDQPADQPADRMQDDISSEQYPLFDKRQKCCTGRK (SEQ IDNO:265) GSCSGKACKNLKCCSGR Toxin Sequence:Xaa2-Lys-Cys-Cys-Thr-Gly-Arg-Lys-Gly-Ser-Cys-Ser-Gly-Lys-Ala-Cys-Lys-Asn-Leu-Lys-Cys-(SEQ ID NO:266) Cys-Ser-# Name:     Bt3.5 Species:  betulinusCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGCTTCTGTTTCCCC (SEQ IDNO:267) TTACTGCTGTTCCGTTGGATGGAGATCAACCTGCAGACCAACCTGCAGAGCGTATGCAGAACGAGCAGCATCCCTCGTTTGATCAGAAAAGAAGGTGCTGCCGGTGGCCATGCCCCAGTATATGCGGCATGGCTAGGTGTTGCTTCGTCATGATAACGTGTTGATGACCA ACTTTCTCGAGTranslation: MMSKLGVLLTICLLLFPLTAVPLDGDQPADQPAERMQNEQHPSFDQKRRCCRWPCPSIC(SEQ ID NO:268) GMARCCFVMITC Toxin Sequence:Arg-Cys-Cys-Arg-Xaa4-Xaa3-Cys-Xaa3-Ser-Ile-Cys-Gly-Met-Ala-Arg-Cys-Cys-Phe-Val-Met(SEQ ID NO:269) Ile-Thr-Cys-{circumflex over ( )} Name:     Bt3.6Species:  betulinus Cloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGATCATCTGTCTGCTTCTGTTTCCCC (SEQ IDNO:270) TTACTGCTGTTCCGCTGGATGGAGATCAGCCTGCAGAGCGTACGCAGATCGAGCAGCATCCCTTGTTTGACCAGAAAAGAAGGTGTTGCCGGTGGCCATGCCCCAGTAGATGCGGCATGGCTAGGTGTTGCTTCGTCATGATAACGTGTTGATGANCGACCTCTCNAG Translation:MMSKLGVLLIICLLLFPLTAVPLDGDQPAERTQIEQHPLFDQKRRCCRWPCPSRCGMAR (SEQ IDNO:271) CCFVMITC Toxin Sequence:Arg-Cys-Cys-Arg-Xaa4-Xaa3-Cys-Xaa3-Ser-Arg-Cys-Gly-Met-Ala-Arg-Cys-Cys-Phe-Val-Met-(SEQ ID NO:272) Ile-Thr-Cys-{circumflex over ( )} Name:     Pr3.1Species:  parius Cloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGCTTCTGTTTCCCC (SEQ IDNO:273) TTACTGCTCTTCCGATGGATGGTGATCAACCTGCAGACCGACTTGTAGAGCGTATGCAGGACAACATTTCATCTGAGCAGCATCCCTTCTTTGAAAAGAGAAGAGGAGGCTGTTGCACACCTCCGAAGAAATGCAAAGACCGAGCCTGCAAACCTGCACGTTGCTGCGGCCCAGGATAACGTGTTGATGACCAACTTTCTCGCC Translation:MMSKLGVLLTICLLLFPLTALPMDGDQPADRLVERMQDNISSEQHPFFEKRRGGCCTPP (SEQ IDNO:274) KKCKDRACKPARCCGPG Toxin Sequence:Arg-Gly-Gly-Cys-Cys-Thr-Xaa3-Xaa3-Lys-Lys-Cys-Lys-Asp-Arg-Ala-Cys-Lys-Xaa3-Ala-Arg-(SEQ ID NO:275) Cys-Cys-Gly-Xaa3-# Name:     Pr3.2 Species:  pariusCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGCTTCTGTTTCCCC (SEQ IDNO:276) TTACTGCTCTTCCGATGGATGGTGATCAACCTGCAGACCGACTTGTAGAGCGTATGCAGGACAACATTTCATCTGAGCAGCATCCCTTCTTTGAAAAGAGAAGAGGCTGTTGCACACCTCCGAGGAAATGCAAAGACCGAGCCTGCAAACCTGCACGTTGTTGCGGCCCAGGATAACGTGTTGATGACCAACTTTCTCGAG Translation:MMSKLGVLLTICLLLFPLTALPMDGDQPADRLVERMQDNISSEQHPFFEKRRGCCTPPR (SEQ IDNO:277) KCKDRACKPARCCGPG Toxin Sequence:Arg-Gly-Cys-Cys-Thr-Xaa3-Xaa3-Arg-Lys-Cys-Lys-Asp-Arg-Ala-Cys-Lys-Xaa3-Ala-Arg-Cys-(SEQ ID NO:278) Cys-Gly-Xaa3-# Name:     Ct3.1 Species:  coronatusCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGCTTCTGTTTCCAA (SEQ IDNO:279) TTACTGCCCTTCCGCTGGATGAAGATCAACCTGCAGACCGACCTGCAGAGCGTATGCAGGACATTGCAACTGAACAGCATCCCTTGTTTGATCCCGTCAAACGGTGCTGCGATTGGCCATGCATCCCAGGATGCACCCCTTGTTGCTTGCCTTGATAACGTGTTGATGACC AACTTTCTCGAGTranslation:MMSKLGVLLTICLLLFPITALPLDEDQPADRPAERMQDIATEQHPLFDPVKRCCDWPCIP (SEQ IDNO:280) GCTPCCLP Toxin Sequence:Cys-Cys-Asp-Xaa4-Xaa3-Cys-Ile-Xaa3-Gly-Cys-Thr-Xaa3-Cys-Cys-Leu-Xaa3-{circumflexover ( )} (SEQ ID NO:281) Name:     Ms3.1 Species:  musicusCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCCTGTTGACCATCTGTCTGCTTCTGTTTCCTC (SEQ IDNO:282) TTTCTGCTCTTCCGATGGATGAAGATCAACTTGCAGACCTACCTGCAGAGCGTATGCGGGACACTGCAACTGTAGATCATCCCTCCTATGATCCTGACAAAGCGTGCTGCGAGCAGAGCTGTACAACATGCTTTCCGTGCTGCTAGCCTTGAACACAGTAACGTGTTGATGACCAACTTTCTCGAG Translation:MMSKLGVLLTICLLLFPLSALPMDEDQLADLPAERMRDTATVDHPSYDPDKACCEQSCT (SEQ IDNO:283) TCFPCC Toxin Sequence:Ala-Cys-Cys-Xaa1-Gln-Ser-Cys-Thr-Thr-Cys-Phe-Xaa3-Cys-Cys-{circumflexover ( )} (SEQ ID NO:284) Name:     bt3b Species:  betulinus Isolated:Yes Toxin Sequence:Ala-Cys-Cys-Xaa1-Gln-Ser-Cys-Thr-Thr-Cys-Met-Xaa3-Cys-Cys-{circumflexover ( )} (SEQ ID NO:285) Name:     bt3c Species:  betulinus Isolated:Yes Toxin Sequence:Cys-Cys-Xaa1-Gln-Ser-Cys-Thr-Thr-Cys-Met-Xaa3-Cys-Cys-Xaa4-? (SEQ IDNO:286) Name:     Pn3.2 Species:  pennaceus Cloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGCTTCTGTTTCCCC (SEQ IDNO:287) TTACTGCTCTTCCGCTGGATGGAGATCAACCTGCATACCAAGCTGCAGAGCGTATGCAGGCCGAGCATCATCCCTTGTTTGATCAGAAAAGACGGTGCTGCAAGTTTCCATGCCCCGATAGTTGCAAATATTTGTGTTGCGGGTGATGATAACATGTTGATGACCAACTTT CTTGAGTranslation: MMSKLGVLLTICLLLFPLTALPLDGDQPAYQAAERMQAEHHPLFDQKRRCCKFPCPDSC(SEQ ID NO:288) KYLCCG Toxin Sequence:Arg-Cys-Cys-Lys-Phe-Xaa3-Cys-Xaa3-Asp-Ser-Cys-Lys-Xaa5-Leu-Cys-Cys-#(SEQ ID NO:289) Name:     Pu3.2 Species:  pulicarius Cloned:   Yes DNASequence: GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGCTTCTGTTTCCCC(SEQ ID NO:290)TTACTGCTCTTCCGATGGATGGTGATCAACTTGCAGACCGACTTGTAGAGCGTATGCAGGACAACATTTCATCTGAGCAGCATCCCTTCTTTGATCCCGTCAAACGGTGTTGCGTCAGCTGTTACATGGGATGCATCCCTTGTTGCTTCTAGTAATAACGTGTTGATGACC AACTTTCTCGAGTranslation: MMSKLGVLLTICLLLFPLTALPMDGDQLADRLVERMQDNISSEQHPFFDPVKRCCVSCY(SEQ ID NO:291) MGCIIPCCF Toxin Sequence:Cys-Cys-Val-Ser-Cys-Xaa5-Met-Gly-Cys-Ile-Xaa3-Cys-Cys-Phe-{circumflexover ( )} (SEQ ID NO:292) Name:     Pu3.3 Species:  pulicariusCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCGTCTGTCTGCTTCTGTGTCCCC (SEQ IDNO:293) TTACTGCTCTTCCACTGGATGAAGATCAACTTGCAGACCGACCTGCAGAGCGTATGCAGGATGACACTTCAGCTGCACAGATTTTCGGGTTTGATCCCGTCAAACGGTGCTGCAAATTGCTATGCTACTCGGGATGCACTCCTTGTTGCCATATTTGATAACGTGTTGATGACCAACTTTCTCGAG Translation:MMSKLGVLLTVCLLLCPLTALPLDEDQLADRPAERMQDDTSAAQIFGFDPVKRCCKLLC (SEQ IDNO:294) YSGCTPCCHI Toxin Sequence:Cys-Cys-Lys-Leu-Leu-Cys-Xaa5-Ser-Gly-Cys-Thr-Xaa3-Cys-Cys-His-Ile-{circumflexover ( )} (SEQ ID NO:295) Name:     Ra3.2 Species:  rattus Cloned:   YesDNA Sequence: GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGCTTGTGTTTCCGC(SEQ ID NO:296)TTACTGCTCTTCCGATGGATGGTGATCAACCTGCAGACCGACTTGTAGAGCGTATACAGGACAACATTTCATCTGAGCAGCATCCCTTCTTTGAAAAGAGAAGAGGCTGTTGCGCACCTCCGAGGAAATGCAAAGACCGAGCCTGCAAACCTGCACGTTGCTGCGGCCCAGGATAACGTGTTGATGACCAACTTTCTCGAG Translation:MMSKLGVLLTICLLVFPLTALPMDGDQPADRLVERIQDNISSEQHPFFEKRRGCCAPPRK (SEQ IDNO:297) CKDRACKPARCCGPG Toxin Sequence:Arg-Gly-Cys-Cys-Ala-Xaa3-Xaa3-Arg-Lys-Cys-Lys-Asp-Arg-Ala-Cys-Lys-Xaa3-Ala-Arg-Cys-(SEQ ID NO:298) Cys-Gly-Xaa3-# Name:     Sm3.3 Species:  stercusmuscarumCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACAATCTGTCTGCTTCTGTTTCCCC (SEQ IDNO:299) TTATTGCTCTTCCGCTGGATGGAGATCAACCTGCAGACCGACCTGCAGAGCGTATGCAGGACGACATTTCATCTGAGAAGCATCCCTTGTTTGATAAGAGACAACGGTGTTGCAATGGGCGGAGGGGATGCTCCAGCAGATGGTGCAGAGATCACTCACGTTGTTGCGGTCGACGATAACGTGTTGATGACCAACTTTCTCGAG Translation:MMSKLGVLLTICLLLFPLIALPLDGDQPADRPAERMQDDISSEKHPLFDKRQRCCNGRRG (SEQ IDNO:300) CSSRWCRDHSRCCGRR Toxin Sequence:Xaa2-Arg-Cys-Cys-Asn-Gly-Arg-Arg-Gly-Cys-Ser-Ser-Arg-Xaa4-Cys-Arg-Asp-His-Ser-Arg-(SEQ ID NO:301) Cys-Cys-# Name:     Eb3.1 Species:  ebraeusCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGCTTCTGTTTCCCC (SEQ IDNO:302) TTACTGCTCTTCCACTGGATGAAGGTCAACCTGCAGACCTACCTGCAGAGCGTATGCAGGACATTGCAACTGAACAGCATCCCTTGTTTGATCCTGTCAAACGGTGTTGCGAGCAGCCATGCTACATGGGATGCATCCCTTGTTGCTTCTAATAATAACGTGTTGATGACC AACTTTCTCGAGTranslation: MMSKLGVLLTICLLLFPLTALPLDEGQPADLPAERMQDIATEQHPLFDPVKRCCEQPCY(SEQ ID NO:303) MGCIPCCF Toxin Sequence:Cys-Cys-Xaa1-Gln-Xaa3-Cys-Xaa5-Met-Gly-Cys-Ile-Xaa3-Cys-Cys-Phe-{circumflexover ( )} (SEQ ID NO:304) Name:     Eb3.2 Species:  ebraeusCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGCTTCTGTTTCCCC (SEQ IDNO:305) TTACTGCTCTTCCACTGGATGAAGATCAACCTGCAGACCTACCTGCAGAGCGTATGCAGGACATTGCAACTGAACAGCATCCCTTGTTTGATCCTGTCAAACGGTGCTGCGCGCAGCCATGCTACATGGGATGCATCCCTTGTTGCTTCTAATAATAACGTGTTGATGACC AACTTTCTCGAGTranslation: MMSKLGVLLTICLLLFPLTALPLDEDQPADLPAERMQDIATEQHPLFDPVKRCCAQPCY(SEQ ID NO:306) MGCIPCCF Toxin Sequence:Cys-Cys-Ala-Gln-Xaa3-Cys-Xaa5-Met-Gly-Cys-Ile-Xaa3-Cys-Cys-Phe-{circumflexover ( )} (SEQ ID NO:307) Name:     Fd3.2 Species:  flavidusCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGCTTCTGTTTCCCC (SEQ IDNO:308) TTACTGCTGTTCCGTTGGATGGAGATCAACCTGCAGACCAGCCTGCAGAGCGTATGCAGAACGAGCAGCATCCCTTGTTTGATCAGAAAAGAAGGTGCTGCCGGTGGCCATGCCCCAGTATATGCGGCATGGCTAGGTGTTGCTCGTCATGATAACGTGTTGATGACCAA CTTTCTCGAGTranslation: MMSKLGVLLTICLLLFPLTAVPLDGDQPADQPAERMQNEQHPLFDQKRRCCRWPCPSIC(SEQ ID NO:309) GMARCCSS Toxin Sequence:Arg-Cys-Cys-Arg-Xaa4-Xaa3-Cys-Xaa3-Ser-Ile-Cys-Gly-Met-Ala-Arg-Cys-Cys-Ser-Ser-{circumflexover ( )} (SEQ ID NO:310) Name:     Mf3.1 Species:  miliarisCloned:   Yes DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTGTCTGCTTCTGTTTCCAA (SEQ IDNO:311) TTACTGCCCTTCCACTGGATGAAGATCAACCTGCAGACCGACCTGCAGAGCGTATGCAGGACATTGCAACTGAACAGCATCCCTTGTTTGATCCCGTCAAACGGTGTTGCGATTGGCCATGCAGCGCAGGATGCTACCCTTGTTGCTTCCCTTAATAACGTGTTGATGACCAACTNANGNAAAAAAA Translation:MMSKLGVLLTICLLLFPITALPLDEDQPADRPAERMQDIATEQHPLFDPVKRCCDWPCSA (SEQ IDNO:312) GCYPCCFP Toxin Sequence:Cys-Cys-Asp-Xaa4-Xaa3-Cys-Ser-Ala-Gly-Cys-Xaa5-Xaa3-Cys-Cys-Phe-Xaa3-{circumflexover ( )} (SEQ ID NO:313) Name:     Mf3.2 Species:  miliarisCloned:   Yes Notes: DNA Sequence:GGATCCATGATGTCTAAACTGGGAGTGGTGCCATTCGTCTTTCTGGTCCTGTTTCCCC (SEQ IDNO:314) TGGCAACACTCCAACTGGATGCAGATCAACCTGCAGACCGACCTGCGCGTAAAAAGGGCATTGCAACTAAACGGCATCCCTTGTCTGATCCTGTCAGAGGGTGTTGCCCTCCAATGTGCACACCATGCTTCCCTTGCTGTTTTCGTTAATAACGTGTTGATGNATGATGN ANTranslation:MMSKLGVVPFVFLVLFPLATLQLDADQPADRPARKKGIATKRHPLSDPVRGCCPPMCTPCFPCC (SEQ IDNO:315) FR Toxin Sequence:Gly-Cys-Cys-Xaa3-Xaa3-Met-Cys-Thr-Xaa3-Cys-Phe-Xaa3-Cys-Cys-Phe-Arg-{circumflexover ( )} (SEQ ID NO:316) Name:     Af3.1 Species:  ammiralisCloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ IDNO:317) TCTGCTTCTGTTTCCCCTTACTGCTCTTCCGCTGGATGGAGATCAACCTGCAGACCAAGCTGCAGAGCGTATGCAGGCCGAGCAGCATCCCTTGTTTGATCAGAAAAGACGGTGTTGCAGGTTTCCATGCCCCGATACTTGCAGACATTTGTGTTGCGGGTGATGATAACGTGCTGATGACCCACTTTGTCATCACGGCTACGTCAAGTGTCTAATGAATAAGTAAA ATGATTGCAGTTranslation: MMSKLGVLLTICLLLFPLTALPLDGDQPADQAAERMQAEQHPLFDQKRRCCRFPCPDTC(SEQ ID NO:318) RHLCCG Toxin Sequence:Arg-Cys-Cys-Arg-Phe-Xaa3-Cys-Xaa3-Asp-Thr-Cys-Arg-His-Leu-Cys-Cys-# (SEQID NO:319) Name:     Af3.2 Species:  ammiralis Cloned:   Yes DNASequence: CAAGAGGGATCGATAGCAGTTCATGATGTTTAAACTGGGAGTCTTGCTGACCATCTG (SEQID NO:320) TCTACTTCTGTTTTCCCTTAATGCTGTTCCGCTGGATGGAGATCAACCTGCAGACCAACCTGCAGAGCGTCTGCTGGACGACATTTCATCTGAAAATAATCCCTTTTATGATCCCGCCAAACGGTGTTGCATGACTTGCTTCGGTTGCACACCTTGTTGTGGATGACCAGCCTCATCAAGTGTCTAACGAATAAGTAAAACGATTGCAGT Translation:MMFKLGVLLTICLLLFSLNAVPLDGDQPADQPAERLLDDISSENNPFYDPAKRCCMTCF (SEQ IDNO:321) GCTPCCG Toxin Sequence:Cys-Cys-Met-Thr-Cys-Phe-Gly-Cys-Thr-Xaa3-Cys-Cys-# (SEQ ID NO:322)Name:     Af3.3 Species:  ammiralis Cloned:   Yes DNA Sequence:CAAGAAGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGCCTTGTTGACCATCT (SEQ ID NO:323)GTCTACTTCTGTTTTCCCTTACTGCTGTTCCGCTGGATGGAGATCAACATGCAGACCAACCTGCAGAGCGTCTGCAGGACCGCCTTCCAACTGAAAATCATCCCTTATATGATCCCGTCAAACGGTGTTGCGATGATTCGGAATGCGACTATTCTTGCTGGCCTTGCTGTATTTTTTCATAACCTTTGTTATCGCGGCCTCATCCTAGTGTCAAATGAATAAGTAAAA CGATTGCAGTTranslation: MMSKLGALLTICLLLFSLTAVPLDGDQHADQPAERLQDRLPTENHPLYDPVKRCCDDSE(SEQ ID NO:324) CDYSCWPCCIFS Toxin Sequence:Cys-Cys-Asp-Asp-Ser-Xaa1-Cys-Asp-Xaa5-Ser-Cys-Xaa4-Xaa3-Cys-Cys-Ile-Phe-Ser-{circumflexover ( )} (SEQ ID NO:325) Name:     Af3.4 Species:  ammiralisCloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTTTAAACTCGGAGTCTTGCTGACCATCTG (SEQ IDNO:326) TCTACTTCTGTTTTCCCTAATtGCTGTTCCGCTGGATGGAGATCAACATGCAGACCAACCTGCAGAGCGTCTGCAGGACCGCCTTCCAACTGAAAATCATCCCTTATATGATCCCGTCAAACGGTGTTGCAGGTTGTTATGCCTCAGTTGCAACCCTTGTTGTGGATGACCAGCTTTGTTATCACGGCCTCATCAAGTGTCTAATGAATAAGTAAAACGATTGCAGT Translation:MMFKLGVLLTICLLLFSLIAVPLDGDQHADQPAERLQDRLPTENHPLYDPVKRCCRLLCL (SEQ IDNO:327) SCNPCCG Toxin Sequence:Cys-Cys-Arg-Leu-Leu-Cys-Leu-Ser-Cys-Asn-Xaa3-Cys-Cys-# (SEQ ID NO:328)Name:     Af3.6 Species:  ammiralis Cloned:   Yes DNA Sequence:CAAGAAGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGCCTTGTTGACCATCT (SEQ ID NO:329)GTCTACTTCTGTTTTCCCTTACTGCTGTTCCGCTGGATGGAGATCAACATGCAGACCAACCTGCAGAGCGTCTGCAGGACCGCATTCCAACTGAAGATCATCCCTTATTTGATCCCAACAAACGGTGTTGCGATGATTCGGAATGCGGCTATTCATGCTGGCCTTGCTGTTATGGATAAGCTTTGTTATCGCGGCCTCATCCAGTGTCAACGAATAAGTAAAACGATT GCAGTTranslation:MMSKLGALLTICLLLFSLTAVPLDGDQHADQPAERLQDRIPTEDHPLFDPNKRCCDDSEC (SEQ IDNO:330) GYSCWPCCYG Toxin Sequence:Cys-Cys-Asp-Asp-Ser-Xaa1-Cys-Gly-Xaa5-Ser-Cys-Xaa4-Xaa3-Cys-Cys-Xaa5-#(SEQ ID NO:331) Name:     Sf3.1 Species:  spurius Cloned:   Yes DNASequence: CAAGAAGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGCTGACCATCT (SEQID NO:332) GTCTGCTTCTGTTTCCACGTACTTCTCTTCCGCTGGATGGAGATCAACCTGCAGTCCGATCTGCAAAGCGTATGCATTCATCTATACAGCGTCGTTTCTTTGATCCCGTCAAACGGTGTTGCCCTAGATGCAGCGAGTGCAACCCTTGTTGTGGATGACCAGCTTTGTCATCGCGGCCTCATTAAGTGTCTAATGAATAAGTAAAATGATTGCAGT Translation:MMSKLGVLLTICLLLFPRTSLPLDGDQPAVRSAKRMHSSIQRRFFDPVKRCCPRCSECNP (SEQ IDNO:333) CCG Toxin Sequence:Cys-Cys-Xaa3-Arg-Cys-Ser-Xaa1-Cys-Asn-Xaa3-Cys-Cys-# (SEQ ID NO:334)Name:     Om3.1 Species:  omaria Cloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTCGTTGACCATCT (SEQ ID NO:335)GTCTACTTCTATTTTCCCTTACTGCTGTTCCGCTTGATGGAGATCAACATGCAGACCAACCTGCAGAGCGTCTGCAGGGCGACATTTTATCTGAAAAGCATCCCTTATTTAATCCCGTCAAACGGTGTTGCGATGAGGAAGAATGCAGCAGTGCATGCTGGCCTTGTTGTTGGGGGTGATCAGCTTTGTTATCGCGGCCTCATCAAGTGTCTAATGAATAAGTAAAAT GATTGCAGTTranslation:MMSKLGVSLTICLLLFSLTAVPLDGDQHADQPAERLQGDILSEKHPLFNPVKRCCDEEEC (SEQ IDNO:336) SSACWPCCWG Toxin Sequence:Cys-Cys-Asp-Xaa1-Xaa1-Xaa1-Cys-Ser-Ser-Ala-Cys-Xaa4-Xaa3-Cys-Cys-Xaa4-#(SEQ ID NO:337) Name:     Om3.2 Species:  omaria Cloned:   Yes DNASequence: CAAGAAGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGATCATCTG (SEQID NO:338) TCTACTTCTGTGTCCCCTTACTGCTGTTCTGGAGGATGGAGATCAACCTGCAGACCGACCTGCAGAGCGTATGCAGGACGACATTTCAACTGAGCATCATCCCTTTTATGATCCCGTCAAACGGTGTTGCAAGTACGGGTGGACATGCTTGCTAGGATGCACTCCTTGTGATTGTTGACCAGTTTTGTTATCGCGGCCTCGTCAAGTGTCTAATGAATAAGTAAAACG ATTGCAGTTranslation: MMSKLGVLLIICLLLCPLTAVLEDGDQPADRPAERMQDDISTEHHPFYDPVKRCCKYGW(SEQ ID NO:339) TCLLGCTPCDC Toxin Sequence:Cys-Cys-Lys-Xaa5-Gly-Xaa4-Thr-Cys-Leu-Leu-Gly-Cys-Thr-Xaa3-Cys-Asp-Cys-{circumflexover ( )} (SEQ ID NO:340) Name:     Om3.3 Species:  omaria Cloned:   YesDNA Sequence: CAAGAGGGATCGATAGCAGTTCATGATGTCTATACTGGGAGTCTTGTTGATCATCTG(SEQ ID NO:341)TCTACTTCTGTGTCCCCTTACTGCTGTTCTGGAGGATGGAGATCAACCTGCAGACCGACCTGCAGAGCGTATGCAGGACGGCATTTCATCTGAACATCATCCCTTTTTGGATCCCGTCAAACGGTGTTGCCATCTATTGGCATGCCGCTTTGGATGCTCGCCTTGTTGTTGGTGACCAGCTTTGTTATCGCGGCCTCATCAAGTGTCTAATGAATAAGTAAAACGATT GCAGTTranslation:MMSILGVLLIICLLLCPLTAVLEDGDQPADRPAERMQDGISSEHHPFLDPVKRCCHLLAC (SEQ IDNO:342) RFGCSPCCW Toxin Sequence:Cys-Cys-His-Leu-Leu-Ala-Cys-Arg-Phe-Gly-Cys-Ser-Xaa3-Cys-Cys-Xaa4-{circumflexover ( )} (SEQ ID NO:343) Name:     Om3.4 Species:  omaria Cloned:   YesDNA Sequence: CAAGAAGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGATCATCTG(SEQ ID NO:344)TCTACTTCTTTGTCCCCTTACTGCTGTTCCGCAGGATGGAGATCAACCTGCAGACCGACCTGCAGAGCGTATGCAGGGCGGCATTTCATCTGAACATCATCCCTTTTTTGATCCCGTCAAACGGTGTTGCAGGTACGGGTGGACATGCTGGCTAGGATGCACTCCCTGTGGTTGTTGACCAGCTTTGTTATCGCGGCCTCATCAAGTGTCTAATGAATAAGTAAAAC GATTGCAGTTranslation: MMSKLGVLLIICLLLCPLTAVPQDGDQPADRPAERMQGGISSEHHPFFDPVKRCCRYGW(SEQ ID NO:345) TCWLGCTPCGC Toxin Sequence:Cys-Cys-Arg-Xaa5-Gly-Xaa4-Thr-Cys-Xaa4-Leu-Gly-Cys-Thr-Xaa3-Cys-Gly-Cys-{circumflexover ( )} (SEQ ID NO:346) Name:     Ep3.1 Species:  episcopatusCloned:   Yes DNA Sequence:CAAGAAGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ IDNO:347) TCTACTTCTGTTTTCCCTTATTGCTGTTCCGCTTGATGGAGATCAACATGCAGACCAACCTGCAGAGCGTCTGCAGGGCGACATTTTATCTGAAAAGCATCCCTTATTTATGCCTGTCAAACGGTGTTGCGATGAGGACGAATGCAACAGTTCATGCTGGCCTTGTTGTTGGGGGTGATCAGCTTTGTTATCGCGGCCTGATCAAGTGTATAATGAATAAGTAAAACG ATTGCAGTTranslation:MMSKLGVLLTICLLLFSLIAVPLDGDQHADQPAERLQGDILSEKHPLFMPVKRCCDEDEC (SEQ IDNO:348) NSSCWPCCWG Toxin Sequence:Cys-Cys-Asp-Xaa1-Asp-Xaa1-Cys-Asn-Ser-Ser-Cys-Xaa4-Xaa3-Cys-Cys-Xaa4-#(SEQ ID NO:349) Name:     Ep3.2 Species:  episcopatus Cloned:   Yes DNASequence: CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQID NO:350) TCTACTTCTGTTTTCCCTTATTGCTGTTCCGCTTGATGGAGATCAACATGCAGACCAACCTGCAGAGCGTCTGCAGGGCGACATTTTATCTGAAAAGCATCCCTTATTTATGCCTGTCAAACGGTGTTGCGATGAGGACGAATGCAGCAGTTCATGCTGGCCTTGTTGTTGGGGATGAGCAGCTTTGTTATCGCGGCCTCATCAAGTGTCTAATGAATAAGTAAAACG ATTGCAGTTranslation:MMSKLGVLLTICLLLFSLIAVPLDGDQHADQPAERLQGDILSEKHPLFMPVKRCCDEDEC (SEQ IDNO:351) SSSCWPCCWG Toxin Sequence:Cys-Cys-Asp-Xaa1-Asp-Xaa1-Cys-Ser-Ser-Ser-Cys-Xaa4-Xaa3-Cys-Cys-Xaa4-#(SEQ ID NO:352) Name:     Ep3.3 Species:  episcopatus Cloned:   Yes DNASequence: CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQID NO:353) TCTACTTCTGTTTTCCCTTACTGCTGTTCCGCTTGATGGAGATCAACATGCAGACCAACCTGCAGAGCGTCTGCAGGGCGACATTTTATCTGAAAAGCATCCCTTATTTAATCCCGTCAAACGGTGTTGCCCGGCGGCGGCATGTGCCATGGGATGCAAGCCTTGTTGTGGATGAGCAGCTTTGTTATCGTGGCCTCATCAAGTGTCTAATGAATAAGTAAAACGATT GCAGTTranslation: MMSKLGVLLTICLLLFSLTAVPLDGDQHADQPAERLQGDILSEKHPLFNPVKRCCPAAA(SEQ ID NO:354) CAMGCKPCCG Toxin Sequence:Cys-Cys-Xaa3-Ala-Ala-Ala-Cys-Ala-Met-Gly-Cys-Lys-Xaa3-Cys-Cys-# (SEQ IDNO:355) Name:     Au3.2 Species:  aulicus Cloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ IDNO:356) TCTGCTTCTGTTTTCCGTTACTGCTCTTCCGCCGGATGGAGATCAACCTGCAGACCGAGCTGCAGAGCGTAGGCAGGTCGAGCAGCATCCCGTGTTTGATCATGAAAGAGGGTGTTGCTCGCCACCATGCCACAGTATTTGCGCTGCTTTCTGTTGCGGGTGATGATAACGTGTTGATGACCCACTTTGTCATCACGGCTGCGTCAAGTGTCTAATGAATAAGTAAA ATGATTGCAGTTranslation: MMSKLGVLLTICLLLFSVTALPPDGDQPADRAAERRQVEQHPVFDHERGCCSPPCHSIC(SEQ ID NO:357) AAFCCG Toxin Sequence:Gly-Cys-Cys-Ser-Xaa3-Xaa3-Cys-His-Ser-Ile-Cys-Ala-Ala-Phe-Cys-Cys-# (SEQID NO:358) Name:     Au3.3 Species:  aulicus Cloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ IDNO:359) TCTACTTCTGTTTTCCCTTACTGCTGTTCCGCTTGATGGAGATCAACATGCAGACCAACCTGCAGAGCGTCTGCAGGGCGACATTTTATCTGAAAAGCATCCCTTATTTAATCCCGTCAAACGGTGTTGCCGACCGGTGGCATGTGCCATGGGATGCAAGCCTTGTTGTGGATGAGCAGCTTTGTTATCGTGGCCTCATCAAGTGTCTAATGAATAAGTAAAATGATT GCAGTTranslation: MMSKLGVLLTICLLLFSLTAVPLDGDQHADQPAERLQGDILSEKHPLFNPVKRCCRPVA(SEQ ID NO:360) CAMGCKPCCG Toxin Sequence:Cys-Cys-Arg-Xaa3-Val-Ala-Cys-Ala-Met-Gly-Cys-Lys-Xaa3-Cys-Cys-# (SEQ IDNO:361) Name:     Au3.4 Species:  aulicus Cloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCaTGATGTCTAAACTGGGAGTCTTGTTGATCATCTG (SEQ IDNO:362) TCTACTTCTGTCTCCCCTTACTGCTGTTCCGCTGGATGGAGATCAACCTGCAGACCGACCTGCAGAGCGTATGCAGGACGACATTTCATCTGAACATCAACCCATGTTTGATGCCATCAGACAGTGTTGCCCGGCGGTGGCATGCGCCATGGGATGCGAGCCTTGTTGTGGATGACCAGCTTTGTTATCGCGGCCTCATCAAGTGTCTAATGAATAAGTAAAATGAT TGCAGTTranslation:MMSKLGVLLIICLLLSPLTAVPLDGDQPADRPAERMQDDISSEHQPMFDAIRQCCPAVAC (SEQ IDNO:363) AMGCEPCCG Toxin Sequence:Xaa2-Cys-Cys-Xaa3-Ala-Val-Ala-Cys-Ala-Met-Gly-Cys-Xaa1-Xaa3-Cys-Cys-#(SEQ ID NO:364) Name:     Ae3.1 Species:  aureus Cloned:   Yes DNASequence: CAAGAAGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGCCTTGTTGACCATCT (SEQID NO:365) GTCTACTTCTGTTTTCCCTTACTGCTGTTCCGCTGGATGGAGATCAACATGCAGACCAACATGCAGAGCGTCTGCATGACCGCCTTCCAACTGAAAATCATCCCTTATATGATCCCGTCAAACGGTGTTGCGATGATTCGGAATGCGACTATTCTTGCTGGCCTTGCTGTATTTTTGGATAACCTTTGTTATCGCGGCCTCATCAAGTGTCAAATGAATAAGTAAAAC GATTGCAGTTranslation: MMSKLGALLTICLLLFSLTAVPLDGDQHADQHAERLHDRLPTENHPLYDPVKRCCDDSE(SEQ ID NO:366) CDYSCWPCCIFG Toxin Sequence:Cys-Cys-Asp-Asp-Ser-Xaa1-Cys-Asp-Xaa5-Ser-Cys-Xaa4-Xaa3-Cys-Cys-Ile-Phe-#(SEQ ID NO:367) Name:     Ae3.2 Species:  aureus Cloned:   Yes DNASequence: CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGCCTTGTTGACCATCT (SEQID NO:368) GTCTACTTCTGTTTTCCCTAACTGCTGTTCCGCTGGATGGAGATCAACATGCAGACCAACCTGCAGAGCGTCTGCAGGACCGCATTCCAACTGAAAATCATCCCTTATTTGATCCGAACAAACGGTGTTGCAATGATTGGGAATGCGACGATTCATGCTGGCCTTGCTGTTATGGATAACCTTTGTTATCGCGGCCTCATCAAGTGTCAAATGAATAAGTAAAACGAT TGCAGTTranslation: MMSKLGALLTICLLLFSLTAVPLDGDQHADQPAERLQDRIPTENHPLFDPNKRCCNDWE(SEQ ID NO:369) CDDSCWPCCYG Toxin Sequence:Cys-Cys-Asn-Asp-Xaa4-Xaa1-Cys-Asp-Asp-Ser-Cys-Xaa4-Xaa3-Cys-Cys-Xaa5-#(SEQ ID NO:370) Name:     Cn3.1 Species:  consors Cloned:   Yes DNASequence: CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQID NO:371) TTTGCTTCTGTTTCCCCTTACTGCTCTTCCAATGGATGGAGATCAATCTGTAGACCGACCTGCAGAGCGTATGCAGGACGACATTTCATCTGAGCTGCATCCCTTGTTCAATCAGAAAAGAATGTGTTGCGGCGAAGGTGCGCCATGCCCCAGCTATTTCAGAAACAGTCAGATTTGTCATTGTTGTTAAATGACAACGTGTCGATGACCAACTTCGTTATCACGACTAATGAATAAGTAAAATGATTGCAGT Translation:MMSKLGVLLTICLLLFPLTALPMDGDQSVDRPAERMQDDISSELHPLFNQKRMCCGEGA (SEQ IDNO:372) PCPSYFRNSQICHCC Toxin Sequence:Met-Cys-Cys-Gly-Xaa1-Gly-Ala-Xaa3-Cys-Xaa3-Ser-Xaa5-Phe-Arg-Asn-Ser-Gln-Ile-Cys-His-(SEQ ID NO:373) Cys-Cys-{circumflex over ( )} Name:     Cn3.3Species:  consors Cloned:   Yes DNA Sequence:TAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACCATCTG (SEQ IDNO:374) TCTGCTTCTGTTTCCCCTTATTGCTCTTCCAATGGATGGAGATCAACCTGCAGACCGACCTGCAGAGCGTATGCAgGACGACATTTCATCTCAGCAGCATCCCTTGTTTGATAAGAGAGGCCGCTGTTGCGATGTGCCGAACGCATGCTCCGGCAGATGGTGCAGAGATCACGCACAATGTTGCGGATGACGATAACGTGTTGATGACCAACTTTGTGATCACGGCTACATCAAGTGAATAAGTAAAACGATTGCAGT Translation:MMSKLGVLLTICLLLFPLIALPMDGDQPADRPAERMQDDISSQQHPLFDKRGRCCDVPN (SEQ IDNO:375) ACSGRWCRDHAQCCG Toxin Sequence:Gly-Arg-Cys-Cys-Asp-Val-Xaa3-Asn-Ala-Cys-Ser-Gly-Arg-Xaa4-Cys-Arg-Asp-His-Ala-Gln-(SEQ ID NO:376) Cys-Cys-# Name:     Cn3.4 Species:  consorsCloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGTTGACTGTCTG (SEQ IDNO:377) TTTGCTTCTGTTTCCCCTTACTGCTCTTCCGATGGATGGAGATCAACCTGCAGACCAACCTGCAGAGCGTATGCAGGACGACATTTCATCTGAGCAGCATCCCTTGTTTGATAAGAGACAAAGGTGTTGCACTGGGAAGAAGGGGTCATGCTCCGGTAAAGCATGCAAAAGTCTCAAATGTTGCTCTGGACGATAACGTGTTGATGACCAACTTTGTTATCACGGCTACGTCAAGTGTCTAGTGAATAAGTAAAACGATTGCAGT Translation:MMSKLGVLLTVCLLLFPLTALPMDGDQPADQPAERMQDDISSEQHPLFDKRQRCCTGK (SEQ IDNO:378) KGSCSGKACKSLKCCSGR Toxin Sequence:Xaa2-Arg-Cys-Cys-Thr-Gly-Lys-Lys-Gly-Ser-Cys-Ser-Gly-Lys-Ala-Cys-Lys-Ser-Leu-Lys-(SEQ ID NO:379) Cys-Cys-Ser-# Name:     Em3.1 Species:  emaciatusCloned:   Yes DNA Sequence:CAAGAGGGATCGATAGCAGTTCATGATGTCTAAACTGGGAGTCTTGCTGACCATCTGTCTGCTTCTGTT(SEQ ID NO:380)TCCCCTTACTGTTCTTCCGATGGATGGAGATCAACCTGCAGACCTACCTGCATTGCGTGCGCAGTTCTTTGCACCTGAACATAGTCCCCGGTTTGACCCCGTCAAACGGTGCTGCTCGCGGGATTGCAGTGTTTGCATCCCTTGTTGCCCGTATGGATCACCTTGATTATTGCGGCCACGTCAAGTGTCTAATGAATAAGTAAAATGATTGCAGT Translation:MMSKLGVLLTICLLLFPLTVLPMDGDQPADLPALRAQFFAPEHSPRFDPVKRCCSRDCSVCIPCCPYGSP(SEQ ID NO:381) Toxin Sequence:Cys-Cys-Ser-Arg-Asp-Cys-Ser-Val-Cys-Ile-Xaa3-Cys-Cys-Xaa3-Xaa5-Gly-Ser-Xaa3-{circumflexover ( )} (SEQ ID NO:382) -------------------------------

[0094] TABLE 2 Alignment of μ-Conopeptides (SEQ ID NO:) TYPE 1 A3.4(F283) ---CCKVQ-CES--C---TPCC{circumflex over ( )} (383) Ak3.1 (F585)---CCELP-CGPGFC---VPCC{circumflex over ( )} (384) Ar3.1---CCERP-CNIG-C---VPCC{circumflex over ( )} (385) Bn3.1 (F586)---CCNWP-CSMG-C---IPCCYY{circumflex over ( )} (386) Bt3.1---CCELP-CH-G-C---VPCCWP{circumflex over ( )} (387) Bt3.2---CCGLP-CN-G-C---VPCCWPS{circumflex over ( )} (388) Bt3.3---CCSRN-CAV--C---IPCCPNWPA{circumflex over ( )} (389) bt3a---CCKQS-CTT--C---MPCCW{circumflex over ( )} (390) bt3b--ACCXQS-CTT--C---MPCC{circumflex over ( )} (391) bt3c---CCEQS-CTT--C---MPCCW? (392) Ca3.3 R--CCRYP-CPDS-C--HGSCCYK{circumflexover ( )} (393) Ca3.4 ---CCPPVACNMG-C---KPCC# (394) Ca3.5---CCDDSECDYS-C---WPCCMF# (395) Ca3.6 (F349)---CCRR--CYMG-C---IPCCF{circumflex over ( )} (396) Circling---CCPPVACNMG-C---KPCCG{circumflex over ( )} (397) Comatose/SKQCCHLAACRFG-C---TOCCN{circumflex over ( )} (398) Death Cp3.1 (F594)S--CCR--DCGED-C---VGCCR{circumflex over ( )} (399) Ct3.1 (Z726)---CCDWP-CIPG-C---TPCCLP{circumflex over ( )} (400) Da3.1---CCDDSECDYS-C---WPCCILS{circumflex over ( )} (401) Da3.2Z-QCCPPVACNMG-C---EPCC# (402) Da3.3 ---CCNAGFCRFG-C---TPCCW{circumflexover ( )} (403) Di3.1 Z--CCVHP-C-P---C---TPCCR{circumflex over ( )}(404) Fi3.1 ---CCPWP--CNIG-C---VPCC{circumflex over ( )} (405) Fi3.2---CCSKN-CAV--C---IPCCP{circumflex over ( )} (406) Fi3.3---CCRWP-CP-ARC---GSCCL{circumflex over ( )} (407) Fi3.4---CCELSRCL-G-C---VPCCTS{circumflex over ( )} (408) Fi3.5---CCELSKCH-G-C---VPCCIP{circumflex over ( )} (409) Ge3.1 (F590)Z--CCTF--CNFG-C---QPCCVP{circumflex over ( )} (410) Ge3.2 (F343/Z--CCTF--CNFG-C---QPCCLT{circumflex over ( )} (411) Z734) Ge3.3 (F590Z--CCTF--CNFG-C---QPCCVP{circumflex over ( )} (412) Gm3.1----CCDDSECDYS-C---WPCCMF# (413) Gm3.2G--CCHLLACRFG-C---SPCCW{circumflex over ( )} (414) Gm3.3---CCSWDVCDHPSC---T-CCG# (415) La3.1 ---CCDWP-CS-G-C---IPCC{circumflexover ( )} (416) Lp3.1 (F340) ZINCCPWP-CPST-C--RHQCCH{circumflex over( )} (417) Lv3.1 (F341) ZINCCPWP-CPDS-C--HYQCCH{circumflex over ( )}(418) Mr3.2 ---CCRLS-CGLG-C---HPCC# (419) Mr3.3--ECCGSFACRFG-C---VPCCV{circumflex over ( )} (420) Mr3.4SKQCCHLPACRFG-C---TPCCW{circumflex over ( )} (421) Mr3.5 (F286)-MGCCPFP-CKTS-C--TTLCC# (422) Ms3.1 (Z738)--ACCEQS-CTT--C---FPCC{circumflex over ( )} (423) Nb3.1 (F87)---CCELP-CGPGFC---VPCC{circumflex over ( )} (424) Pu3.1 (F339)---CCN-S-CYMG-C---IPCCF{circumflex over ( )} (425) Qc3.1 (F342)ZR-CCQWP-CPGS-C----RCCRT# (426) Qc3.2ZR-CCRWP-CPGS-C----RCCRYR{circumflex over ( )} (427) Qc3.3R--CCRYP-CPDS-C--HGSCCYK{circumflex over ( )} (428) QcIIIA---CCSQD-CLV--C---IOCCPN# (429) QcIIIB ---CCSRH-CWV--C---IOCCPN? (430)Ra3.1 (F351) Z-TCCS-N-CGED-C---DGCCQ{circumflex over ( )} (431)Scratcher I ---CCR-T-C-FG-C---TOCC# (433) Ts3.1 (F592)---CCH-K-CYMG-C---IPCCI{circumflex over ( )} (434) Ts3.2 (F345)K--CCRPP-CAMS-C-GMARCCY{circumflex over ( )} (435) Bt3.5 (Z495)R--CCRWP-CPSI-C-GMARCCFVMITC{circumflex over ( )} (436) Bt3.6 (Z497)R--CCRWP-CP-SRC-GMARCCFVMITC{circumflex over ( )} (437) Tx3.1F--CCDSNWCHISDC----ECCY# (438) U014 ---CCHWNWCDHL-C----SCCGS{circumflexover ( )} (439) U017 --DCCOLPACPFG-C---NOCC# (440) U019---CCAPSACRLG-C---ROCCR{circumflex over ( )} (441) U020---CCAOSACRLG-C---ROCCR{circumflex over ( )} (442) U022---CCAPSACRLG-C---RPCCR{circumflex over ( )} (443) U024--GCCGSFACRFG-C---VOCCV{circumflex over ( )} (444) U031---CCSWDVCDHPSC----TCC# (445) U032 (F353) R--CCKFP-CPDS-C--RYLCC# (446)Ae3.1 ---CCDDSECDYS-C---WPCCIF# (447) Ae3.2 ---CCNDWECDDS-C---WPCCY#(448) Af3.1 R--CCR-FPCPDT-C---RHLCC# (449) Af3.2 ---CC--MTC-FG-C---TPCC#(450) Af3.3 ---CCDDSECDYS-C---WPCCIFS{circumflex over ( )} (451) Af3.4---CCR-LLC-LS-C---NPCC# (452) Af3.6 ---CCDDSECGYS-C---WPCCY# (453) Au3.2G--CCS-PPCHSI-C--AAFCC# (454) Au3.3 ---CCRPVACAMG-C---KPCC# (455) Au3.4Z--CCPAVACAMG-C---EPCC# (456) Em3.1---CCS-RDC-SV-C---IPCCPYGSP{circumflex over ( )} (457) Ep3.1---CCDEDECNSS-C---WPCCW# (458) Ep3.2 ---CCDEDECSSS-C---WPCCW# (459)Ep3.3 ---CCPAAACAMG-C---KPCC# (460) Om3.1 ---CCDEEECSSA-C---WPCCW# (461)Om3.3 ---CCHLLACRFG-C---SPCCW{circumflex over ( )} (462) Sf3.1---CC--PRC-SE-C---NPCC# (463) TYPE 2 Pn3.2 (AA049)-RCC--KFP-CPDS-C--KYLCC# (464) Fd3.2 (Z831)-RCC--RWP-CPSI-C-GMARCCSS{circumflex over ( )} (465) Pu3.3 (AA405)--CC--KLL-CYSG-C---TPCCHI{circumflex over ( )} (466) Eb3.1 (Z821)--CC--EQP-CYMG-C---IPCCF{circumflex over ( )} (467) Eb3.2 (Z822)--CC--AQP-CYMG-C---IPCCF{circumflex over ( )} (468) Pu3.2 (AA403)--CC--V-S-CYMG-C---IPCCF{circumflex over ( )} (469) Mf3.1 (Z882)--CC--DWP-CSAG-C---YPCCFP{circumflex over ( )} (470) Mf3.2 (Z885)-GCC---PPM-C-TP-C---FPCCFR{circumflex over ( )} (471) Ra3.2 (AA414)RGCCAPPRK-CKDRACK-PARCCGP# (472) Sm3.3 (AA419) ZRCCNGRRG-CSSRWCRDHSRCC#(473) Cn3.3 GRCCDVPNA-CSGRWCRDHAQCC# (474) Cn3.4ZRCCTGKKGSCSGKACKSL-KCCS# (475) TYPE 3 A3. 1-MCCGEGRKCPSYFRNSQICHCC{circumflex over ( )} (476) A3.2 (F84)--CCR--WPCPRQIDGEY-CGCCL# (477) Bu3.5 -RCCGEGLTCPRYWKNSQICACC{circumflexover ( )} (478) Ca3.1 --CCGPGGSCPVYFRDNFICGCC{circumflex over ( )} (479)Cr3.1 RKCCGKDGPCPKYFKDNFICGCC{circumflex over ( )} (480) E3.1--CCS--WPCPRYSNGKLVCFCCL# (481) M3.2 --CCGPGGSCPVYFRDNFICGCC{circumflexover ( )} (482) M3.3 -MCCGESAPCPSYFRNSQICHCC{circumflex over ( )} (483)M3.4 ZKCCGPGGSCPVYFTDNFICGCC{circumflex over ( )} (484) M3.5ZKCCGPGGSCPVYFRDNFICGCC{circumflex over ( )} (485) S3.1ZKCCGEGSSCPKYFKNNFICGCC{circumflex over ( )} (486) U001ZKCCS-GGSCPLYFRDRLICPCC{circumflex over ( )} (487) U034ZKCCGPGASCPRYFKDNFICGCC{circumflex over ( )} (488) Cn3.1-MCCGEGAPCPSYFRNSQICHCC{circumflex over ( )} (489) TYPE 4 A3.3 (F83)ZK--CCTGK---KGSCSGKACKNL-KCCS# (490) A3.5 (Z488)ZK--CCTGR---KGSCSGKACKNL-KCCS# (491) Bu3.1 VTDRCCK----GKREC-GRWCRDHSRCC#(492) Bu3.1A VGDRCCK----GKRGC-GRWCRDHSRCC# (493) Bu3.2VGERCCK---NGKRGC-GRWCRDHSRCC# (494) Bu3.3 IVDRCCN-KGNGKRGC-SRWCRDHSRCC#(495) Bu3.4 VGLYCCRPKPNGQMMC-DRWCEKNSRCC# (496) Ca3.2-RD-CCTPP---KK-CKDRQCKPQ-RCCA# (497) L3.1 GRD-CCTPP---RK-CRDRACKPQ-RCCG#(498) L3.2 ZRL-CCGFP---KS-CRSRQCKPH-RCC# (499) La3.2-RD-CCTPP---KK--CRDRQCKPA-RCCG# (500) La3.3RPP-CCTYD---GS--CLKESCMRK-ACC# (501) La3.3ARPP-CCTYD---GS-CLKESCKRK-ACC# (502) μ-GIIIA-RD-CCTOO---KK-CKDRQCKOQ-RCCA# (503) μ-GIIIB-RD-CCTOO---RK-CKDRRCKOM-KCCA# (504) μ-GIIIC-RD-CCTOO---KK-CKDRRCKOL-KCCA# (505) μ-PIIIAZRL-CCGFO---KS-CRSRQCKOH-RCC# (506) M3.1 -RD-CCTPP---KK-CKDRQCKPQ-RCCA#(507) Mr3.1 RGG-CCTPP---RK-CKDRACKPA-RCCGP# (508) Nb3.2 (F582)ZK--CCTGK---KGSCSGKACKNL-KCCS# (509) Pr3.1 (Z500)RGG-CCTPP---KK-CKDRACKPA-RCCGP# (510) Pr3.2 (Z501)-RG-CCTPP---RK-CKDPACKPA-RCCGP# (511) R3.1LOS-CCSLN---LRLCOVOACKRN-OCCT# (512) R3.2ZQR-CCTVK----RICOVOACRSK-OCCKS{circumflex over ( )} (513) R3.3RGG-CCTPP---RK-CKDPACKPA-RCCGP# (514) Sm3.1ZK--CCTGK---KGSCSGKACKNL-KCCS# (515) T3.1 H-G-CCKGO---EG-CSSRECROQ--HCC#(516) T3.2 (Y088) H-G-CCEGP---KG-CSSRECRPQ-HCC# (517) Wi3.1 (M548)LPS-CCDFE----RLCVVPACIRH-QCCT# (518) Type 5 Om3.2CCKYGWTCLLGCTPCDC{circumflex over ( )} (519) Om3.4CCRYGWTCWLGCTPCGC{circumflex over ( )} (520) Type 6 S3.2 (F352)Z-NCCNGG-CSSKWCRDHARCC# (432)

Example 3 Effect of Intrathecal Administration of μ-Conopeptides

[0095] Male C57 black mice (20-25 g) are obtained from Charles RiverLaboratories. These mice and the animals are housed in a temperaturecontrolled (23°±3° C.) room with a 12 hour light-dark cycle with freeaccess to food and water. All animals are euthanized in accordance withPublic Health Service policies on the humane care of laboratory animals.

[0096] Intrathecal (it) drug injections are performed as described(Hylden and Wilcox, 1980). A μ-conopeptide or vehicle is administered ina volume of 5 μl. Duration of hind-limb paralysis is assessed. Thisexperiment reveals that injection of μ-conopeptides into the intrathecalspace of C57 black mice produced a paralysis of the animal. The animalsin this experiment recovered fully.

Example 4 Effect of μ-Conopeptides as a Local Anesthetic

[0097] Male Hartley guinea pigs (retired breeders) are obtained formCharles River Laboratories. The local anesthetic test is performedessentially as described (Bulbring and Wajda, 1945). On the day prior totest day, a patch on the back of the guinea pig is denuded of hair,first by shaving with electric clippers and subsequently with depilatorycream (Nair®). Depilatory cream is applied for five minutes and removedwith a warm washcloth. The guinea pigs are dried and returned to theircages. On the following day, intradermal injections (0.1 ml vols) oflidocaine, bupivacaine, a μ-conopeptide or vehicle (0.5% cyclodextran)are made into the denuded patch. The injection produced a raised whealon the surface of the skin which is circled with a felt-tipped pen.Typically, four injections are made on the back of each guinea pig. Insome cases, guinea pigs are reused following at least one week ofrecovery and injecting into an unused portion of the skin. The stimulusconsists of mild pin pricks (not hard enough to break the skin) with a26G needle. The response is a localized skin twitch caused bycontraction of cutaneous muscles. A unit test consisted of six uniformpin pricks, 3-5 seconds apart, within the injected area. Unit scoresrange from 0 (complete anesthesia) to 6 (no anesthesia). For potencyexperiments, the unit test is repeated at each site at five minuteintervals for 30 minutes, and unit test scores summed (with 36representing no anesthesia to 0 representing complete anesthesia. Forduration experiments, unit tests are performed as described over thecourse of several hours to days.

[0098] μ-Conopeptides of the present invention produce a potent and longlasting local anesthetic effect in the intracutaneous wheal test in theguinea pig. As expected, bupivacaine has a slightly longer durationthatn lidocaine, consistent with clinical observations.

Example 5 Muscle Relaxant Effect of μ-Conopeptides in AnesthetizedMonkeys

[0099] μ-Conopeptides are dissolved 0.9 percent saline at aconcentration of 2 mg/ml. Rhesus monkeys are anesthetized withhalothane, nitrous oxide and oxygen. The maintenance concentration ofhalothane is 1.0%. Arterial and venous catheters are placed in thefemoral vessels for drug administration and recording of the arterialpressure. Controlled ventilation is accomplished via an endotrachaeltube. Twitch and tetanic contractions of the tibialis arterior muscleare elicited indirectly via the sciatic nerve. Recordings of arterialpressure electrocardiogram (lead I), heart rate, and muscle function aremade simultaneously. Four to six animals received each listed compound.Four additional animals received succinylcholine chloride ord-tubocurarine chloride as controls. It is seen that the testedμ-conopeptides generally provide similar or better results than thoseseen for succinylcholine chloride or d-tubocurarine chloride.

Example 6 In vivo Activity of μ-Conopeptides in Pain Models

[0100] The anti-pain activity of μ-conopeptides is shown in severalanimal models. These models include the nerve injury model (Chaplan, etal., 1997), the nocioceptive response to s.c. formalin injection in rats(Codene, 1993) and an NMDA-induced persistent pain model (Liu, et al.,1997). In each of these models it is seen that the μ-conopeptides andμ-conopeptides derivatives have analgesic properties.

[0101] More specifically, this study evaluates the effect of intrathecaladministration of μ-conopeptides in mice models of nocioceptive andneuropathic pain. For nocioceptive pain, the effect of theμ-conopeptides is studied in two different tests of inflammatory pain.The first is the formalin test, ideal because it produces a relativelyshort-lived, but reliable pain behavior that is readily quantified.There are two phases of pain behavior, the second of which is presumedto result largely from formalin-evoked inflammation of the hind paw. Aμ-conopeptide is administered 10 minutes prior to injection of formalin.The number of flinches and/or the duration of licking produced by theinjection is monitored. Since the first phase is presumed to be due todirect activation of primary afferents, and thus less dependent on longterm changes in the spinal cord, μ-conopeptides are presumed to havegreatest effect on the magnitude of pain behavior in the second phase.

[0102] The mechanical and thermal thresholds in animals that received aninjection of complete Freund's adjuvant into the hind paw are alsostudied. This produces a localized inflammation including swelling ofthe hind paw and a profound decrease in mechanical and thermalthresholds, that are detected within 24 hours after injection. Thechanges in thresholds in rats that receive μ-conopeptides are comparedwith those of rats that receive vehicle intrathecal injections.

[0103] An important issue is whether the drugs are effective whenadministered after the pain model has been established, or whether theyare effective only if used as a pretreatment. Clearly, the clinical needis for drugs that are effective after the pain has developed. To addressthis issue, animals are studied in which μ-conopeptides are administeredrepeatedly, after the inflammation (CFA) or nerve injury has beenestablished. In these experiments, a μ-conopeptide is injected daily bythe intrathecal (i.t.) route. The mechanical and thermal thresholds(measured, respectively, with von Frey hairs in freely moving animalsand with the Hargreave's test, also in freely moving animals) arerepeated for a 2 to 4 week period after the injury is induced and thechanges in pain measured monitored over time.

Example 7 Effect of μ-Conotoxins in a Pain Model

[0104] Analgesic activity of μ-conotoxins is also tested in pain modelsas follows.

[0105] Persistent pain (formalin test). Intrathecal (it) drug injectionsare performed as described by Hylden and Wilcox (1980). An μ-conopeptideor vehicle is administered in a volume of 5 μl. Fifteen minutes afterthe i.t. injection, the right hindpaw is injected with 20 μl of 5%formalin. Animals are placed in clear plexiglass cylinders backed bymirrors to facilitate observation. Animals are closely observed for 2minutes per 5 minute period, and the amount of time the animal spentlicking the injected paw is recorded in this manner for a total of 45-50minutes. Results are expressed as licking time in seconds per fiveminutes. At the end of the experiment, all animals are placed on anaccelerating rotorod and the latency to first fall was recorded.μ-Conopeptides are found to be active in this model which is predictiveof efficacy for treating neuropathic pain.

[0106] Acute pain (tail-flick). A μ-conopeptide or saline isadministered intrathecally (i.t.) according to the method of Hylden andWilcox (1980) in a constant volume of 5 μl. Mice are gently wrapped in atowel with the tail exposed. At various time-points following the i.t.injection, the tail is dipped in a water bath maintained at 54° C. andthe time to a vigorous tail withdrawal is recorded. If there is nowithdrawal by 8 seconds, the tail is removed to avoid tissue damage.

[0107] Neuropathic pain. The partial sciatic nerve ligation model isused to assess the efficacy of μ-conopeptides in neuropathic pain. Nerveinjury is produced according to the methods of Malmberg and Basbaum(1998). Animals are anesthetized with a ketamine/xylazine solution, thesciatic nerve is exposed and tightly ligated with 8-0 silk suture around⅓ to ½ of the nerve. In sham-operated mice the nerve is exposed, but notligated. Animals are allowed to recover for at least 1 week beforetesting is performed. On the testing day, mice are placed in plexiglasscylinders on a wire mesh frame and allowed to habituate for at least 60minutes. Mechanical allodynia is assessed with calibrated von Freyfilaments using the up-down method as described by Chaplan et al.(1994), and the 50% withdrawal threshold is calculated. Animals that didnot respond to any of the filaments in the series are assigned a maximalvalue of 3.6 grams, which is the filament that typically lifted thehindlimb without bending, and corresponds to approximately {fraction(1/10)} the animal's body weight.

[0108] The data obtained demonstrate that μ-conopeptides have potentanalgesic properties in three commonly used models of pain: acute,persistent/inflammatory and neuropathic pain models.

Example 8 Activity of μ-Conopeptide S3.2 on Neuronal Sodium Channels

[0109] μ-Conopeptide S3.2 was tested for activity on sodium channels asfollows. S3.2 was administered to mice by intracerbroventricular (ICV)injection. Administration of S3.2 in this manner caused mice to show aspectrum of activity that is charcteristic of all sodium channelblockers, including rapid loss of righting reflex, coma-like inactivityand spastic uncontrolled limb movement. Following intrathecal (it)administration to mice, S3.2 causes rapid hindlimb paralysis thatspreads to include the entire body over a course of 10-20 minutesfollowed by death, presumably due to respiratory paralysis. However,unlike classic μ-conopeptides, S3.2 has no significant activityfollowing intravenous administration (iv) to mice. Classicμ-conopeptides, such as GIIIA and PIIIA, cause rapid paralysis and deathfollowing iv administration, indicating their activity at skeletalmuscle sodium channels. To confirm the selectivity of S3.2, 80 nmol wasadministered iv to rats. The effect of S3.2 was measured on skeletalmuscle contraction, blood pressure and heart rate. S3.2 was found tohave no effect on any of these parameters. Controls were performed usingclassical μ-conopeptides, including Sm3.1, Sm3.3 and Bu3.1 describedherein, also administered iv at 80 nmol. These control peptides caused adramatic decrease in skeletal muscle contractility, as well as asignificant drop in systemic blood pressure. Thus, μ-conopeptide S3.2suprisingly is selective for neuronal sodium channels. The most obviousdifference between the S3.2 sequence and the sequences of these otherpeptides is a shortened first loop (the first loop between cysteineresidues) which lacks a charged amino acid.

[0110] It will be appreciated that the methods and compositions of theinstant invention can be incorporated in the form of a variety ofembodiments, only a few of which are disclosed herein. It will beapparent to the artisan that other embodiments exist and do not departfrom the spirit of the invention. Thus, the described embodiments areillustrative and should not be construed as restrictive.

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1 520 1 280 DNA Conus arentus 1 caagaaggat cgatagcagt tcatgatgtctaaactggga gtcttcttga ccatctgtat 60 gcttctgttt ccccttactg ctcttccgctggatggggat caacctgcag accgacctgc 120 agagcgtatg caggacgact ttataactgagcatcatccc ctgtttgatc ctgtcaaacg 180 gtgttgcgag aggccatgca acataggatgcgtaccttgt tgttaatgac cagctttgtc 240 atcgcggcct catcaagcga ataagtaaaacgattgcagt 280 2 67 PRT Conus arentus 2 Met Met Ser Lys Leu Gly Val PheLeu Thr Ile Cys Met Leu Leu Phe 1 5 10 15 Pro Leu Thr Ala Leu Pro LeuAsp Gly Asp Gln Pro Ala Asp Arg Pro 20 25 30 Ala Glu Arg Met Gln Asp AspPhe Ile Thr Glu His His Pro Leu Phe 35 40 45 Asp Pro Val Lys Arg Cys CysGlu Arg Pro Cys Asn Ile Gly Cys Val 50 55 60 Pro Cys Cys 65 3 14 PRTConus arentus PEPTIDE (1)..(14) Xaa at residue 3 is Glu or gamma-carboxyGlu; Xaa at residue 5 and 12 is Pro or Hyp 3 Cys Cys Xaa Arg Xaa Cys AsnIle Gly Cys Val Xaa Cys Cys 1 5 10 4 244 DNA Conus atlanticus 4ggatccatga tgtctaaact gggagtcttg ttgaccatct gtctgcttct gtttccactt 60actgctcttc cgctggatga agatcaaccg gtacaccgac ctgcagagcg tatgcaggac 120atttcatctg atcaacatct cttctttgat ctcatcaaac ggtgctgcga gttgccatgc 180gggccaggct tttgcgtccc ttgttgctga catcaataac gtgttgatga ccaactttct 240cgag 244 5 69 PRT Conus atlanticus 5 Gly Ser Met Met Ser Lys Leu Gly ValLeu Leu Thr Ile Cys Leu Leu 1 5 10 15 Leu Phe Pro Leu Thr Ala Leu ProLeu Asp Glu Asp Gln Pro Val His 20 25 30 Arg Pro Ala Glu Arg Met Gln AspIle Ser Ser Asp Gln His Leu Phe 35 40 45 Phe Asp Leu Ile Lys Arg Cys CysGlu Leu Pro Cys Gly Pro Gly Phe 50 55 60 Cys Val Pro Cys Cys 65 6 15 PRTConus atlanticus PEPTIDE (1)..(15) Xaa at residue 3 is Glu orgamma-carboxy Glu; Xaa at residue 5, 8 and 13 is Pro or Hyp 6 Cys CysXaa Leu Xaa Cys Gly Xaa Gly Phe Cys Val Xaa Cys Cys 1 5 10 15 7 310 DNAConus aurisiacus 7 caagagggat cgatagcagt tcatgatgtc taaactgggagtcttgttga ccatctgttt 60 gcttctgttt ccccttactg ctcttccgat ggatggagatcaatctgtag accgacctga 120 agagcgtatg caggacgaca tttcatctga gcagcatcccttgtttaatc agaaaagaat 180 gtgttgcggc gaaggccgga aatgccccag ctatttcagaaacagtcaga tttgtcattg 240 ttgttaaatg acaacgtgtc gatgaccaac ttcgttatcacgactaatga ataagtaaaa 300 cgattgcagt 310 8 74 PRT Conus aurisiacus 8 MetMet Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15Pro Leu Thr Ala Leu Pro Met Asp Gly Asp Gln Ser Val Asp Arg Pro 20 25 30Glu Glu Arg Met Gln Asp Asp Ile Ser Ser Glu Gln His Pro Leu Phe 35 40 45Asn Gln Lys Arg Met Cys Cys Gly Glu Gly Arg Lys Cys Pro Ser Tyr 50 55 60Phe Arg Asn Ser Gln Ile Cys His Cys Cys 65 70 9 22 PRT Conus aurisiacusPEPTIDE (1)..(22) Xaa at residue 5 is Glu or gamma-carboxy Glu; Xaa atresidue 10 is Pro or Hyp; Xaa at residue 12 is Tyr, 125I-Tyr,mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho- Tyr 9 Met Cys CysGly Xaa Gly Arg Lys Cys Xaa Ser Xaa Phe Arg Asn Ser 1 5 10 15 Gln IleCys His Cys Cys 20 10 257 DNA Conus aurisiacus 10 ggatccatga tgtctaaactgggagtcttg ttgaccatct gtttgcttct gtttcccctt 60 actgctcttc cgatcgatggagatcaatct gtagaccgac ctgcagagcg tatgcaggat 120 gacatttcat ctgagcagcatcgcttgttc aatcagaaaa gaaggtgctg ccggtggcca 180 tgcccccgac aaatcgacggtgaatattgt ggctgttgcc ttggatgata accgtgttga 240 tgaccaactt tctcgag 25711 75 PRT Conus aurisiacus 11 Gly Ser Met Met Ser Lys Leu Gly Val LeuLeu Thr Ile Cys Leu Leu 1 5 10 15 Leu Phe Pro Leu Thr Ala Leu Pro IleAsp Gly Asp Gln Ser Val Asp 20 25 30 Arg Pro Ala Glu Arg Met Gln Asp AspIle Ser Ser Glu Gln His Arg 35 40 45 Leu Phe Asn Gln Lys Arg Arg Cys CysArg Trp Pro Cys Pro Arg Gln 50 55 60 Ile Asp Gly Glu Tyr Cys Gly Cys CysLeu Gly 65 70 75 12 19 PRT Conus aurisiacus PEPTIDE (1)..(19) Xaa atresidue 13 is Glu or gamma-carboxy Glu; Xaa at residue 5 and 7 is Pro orHyp; Xaa at residue 4 is Trp or Bromo Trp; Xaa at residue 14 is Tyr,125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 12Cys Cys Arg Xaa Xaa Cys Xaa Arg Gln Ile Asp Gly Xaa Xaa Cys Gly 1 5 1015 Cys Cys Leu 13 262 DNA Conus aurisiacus 13 ggatccatga tgtctaaactgggagtcttg ttgaccatct gtctacttct gtttcccctt 60 actgcttttc cgatggatggagatcaacct gcagaccaac ctgcagatcg tatgcaggac 120 gacatttcat ctgagcagtatcccttgttt gataagagac aaaagtgttg cactgggaag 180 aaggggtcat gctccggcaaagcatgcaaa aatctcaaat gttgctctgg acgataacgt 240 gttgatgacc aactttctcg ag262 14 78 PRT Conus aurisiacus 14 Gly Ser Met Met Ser Lys Leu Gly ValLeu Leu Thr Ile Cys Leu Leu 1 5 10 15 Leu Phe Pro Leu Thr Ala Phe ProMet Asp Gly Asp Gln Pro Ala Asp 20 25 30 Gln Pro Ala Asp Arg Met Gln AspAsp Ile Ser Ser Glu Gln Tyr Pro 35 40 45 Leu Phe Asp Lys Arg Gln Lys CysCys Thr Gly Lys Lys Gly Ser Cys 50 55 60 Ser Gly Lys Ala Cys Lys Asn LeuLys Cys Cys Ser Gly Arg 65 70 75 15 23 PRT Conus aurisiacus PEPTIDE(1)..(23) Xaa at residue 1 is Gln or pyro-Glu 15 Xaa Lys Cys Cys Thr GlyLys Lys Gly Ser Cys Ser Gly Lys Ala Cys 1 5 10 15 Lys Asn Leu Lys CysCys Ser 20 16 232 DNA Conus aurisiacus 16 ggatccatga tgtctaaactgggagtcttg ctgaccatct gtctgcttct gtttccactt 60 actgctgttc cgctggatggagatcaacct ctagaccgac acgcggagcg tatgcatgat 120 ggcatttcac ctaaacgccatccctggttt gatcccgtca aacggtgttg caaggtgcaa 180 tgcgagtctt gcaccccttgttgctaacgt gttgatgacc aactttctcg ag 232 17 68 PRT Conus aurisiacus 17Gly Ser Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu 1 5 1015 Leu Phe Pro Leu Thr Ala Val Pro Leu Asp Gly Asp Gln Pro Leu Asp 20 2530 Arg His Ala Glu Arg Met His Asp Gly Ile Ser Pro Lys Arg His Pro 35 4045 Trp Phe Asp Pro Val Lys Arg Cys Cys Lys Val Gln Cys Glu Ser Cys 50 5560 Thr Pro Cys Cys 65 18 13 PRT Conus aurisiacus PEPTIDE (1)..(13) Xaaat residue 7 is Glu or gamma-carboxy Glu; Xaa at residue 11 is Pro orHyp 18 Cys Cys Lys Val Gln Cys Xaa Ser Cys Thr Xaa Cys Cys 1 5 10 19 241DNA Conus bandus 19 ggatccatga tgtctaaact gggagtcttg ttgaccatctgtatgcttct gtttcccctc 60 actgctcttc cgatggatgg agatcaacct gcagaccgacctgcagagcg tagtcaggac 120 gtttcatctg aacagcatcc cttgtttgat cccgtcaaacggtgttgcaa ctggccatgc 180 tccatgggat gcatcccttg ttgctactat taataacgtgttgatgacca actttctcga 240 g 241 20 70 PRT Conus bandus 20 Gly Ser MetMet Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Met Leu 1 5 10 15 Leu PhePro Leu Thr Ala Leu Pro Met Asp Gly Asp Gln Pro Ala Asp 20 25 30 Arg ProAla Glu Arg Ser Gln Asp Val Ser Ser Glu Gln His Pro Leu 35 40 45 Phe AspPro Val Lys Arg Cys Cys Asn Trp Pro Cys Ser Met Gly Cys 50 55 60 Ile ProCys Cys Tyr Tyr 65 70 21 16 PRT Conus bandus PEPTIDE (1)..(16) Xaa atresidue 5 and 12 is Pro or Hyp; Xaa at residue 4 is Trp or bromo-Trp;Xaa at residue 15 and 16 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr,O-sulpho-Tyr or O-phospho- Tyr 21 Cys Cys Asn Xaa Xaa Cys Ser Met GlyCys Ile Xaa Cys Cys Xaa Xaa 1 5 10 15 22 298 DNA Conus betulinus 22caagagggat cgatagcagt tcatgatgtc taaactggga gtcttgttga ccttctgtct 60gcttctgttt cccctgactg ctcttccgct ggatgaagat caacctgcag accgacctgc 120agagcgtatg caggacattt catctgaaca gcatcccttg tttgatcccg tcaaacggtg 180ttgcgaattg ccatgccatg gatgcgtccc ttgttgctgg ccttaataac gtgtggatga 240ccaactgtgt tatcacggcc acgtcaagtg tctaatgaat aagtaaaatg attgcagt 298 2367 PRT Conus betulinus 23 Met Met Ser Lys Leu Gly Val Leu Leu Thr PheCys Leu Leu Leu Phe 1 5 10 15 Pro Leu Thr Ala Leu Pro Leu Asp Glu AspGln Pro Ala Asp Arg Pro 20 25 30 Ala Glu Arg Met Gln Asp Ile Ser Ser GluGln His Pro Leu Phe Asp 35 40 45 Pro Val Lys Arg Cys Cys Glu Leu Pro CysHis Gly Cys Val Pro Cys 50 55 60 Cys Trp Pro 65 24 15 PRT Conusbetulinus PEPTIDE (1)..(15) Xaa at residue 3 is Glu or gamma-carboxyGlu; Xaa at residue 5, 11 and 15 is Pro or Hyp; Xaa at residue 14 is Trpor bromo-Trp 24 Cys Cys Xaa Leu Xaa Cys His Gly Cys Val Xaa Cys Cys XaaXaa 1 5 10 15 25 298 DNA Conus betulinus 25 caagagggat cgatagcagttcatgatgtc taaactggga gtcttgttga ccttctgtct 60 gcttctgttt cccctgactgctcttccgct ggatgaagat caacctgcag accgacatgc 120 agagcgtatg caggacatttcacctgaaca gcatccctcg tttgatcccg tcaaacggtg 180 ttgcgggctg ccatgcaatggatgcgtccc ttgttgctgg ccttcataac gtgtggacga 240 ccaactttgt tatcacggccacgtcaagtg tctgatgaat aagtaaaacg attgcagt 298 26 68 PRT Conus betulinus26 Met Met Ser Lys Leu Gly Val Leu Leu Thr Phe Cys Leu Leu Leu Phe 1 510 15 Pro Leu Thr Ala Leu Pro Leu Asp Glu Asp Gln Pro Ala Asp Arg His 2025 30 Ala Glu Arg Met Gln Asp Ile Ser Pro Glu Gln His Pro Ser Phe Asp 3540 45 Pro Val Lys Arg Cys Cys Gly Leu Pro Cys Asn Gly Cys Val Pro Cys 5055 60 Cys Trp Pro Ser 65 27 16 PRT Conus betulinus PEPTIDE (1)..(16) Xaaat residue 5, 11 and 15 is Pro or Hyp; Xaa at residue 14 is Trp orbromo-Trp 27 Cys Cys Gly Leu Xaa Cys Asn Gly Cys Val Xaa Cys Cys Xaa XaaSer 1 5 10 15 28 282 DNA Conus betulinus 28 caagagggat cgatagcagttcatgatgtt taaactggga gtcttgttga ccatctatat 60 gcttctgttt ccctttactgctcttccgct ggatggagat caacctgcag accaacctct 120 agagcgcatg cagtatgacatgttacgtgc agtgaatccc tggtttgatc ccgtcaaaag 180 gtgctgctcg aggaactgcgcagtatgcat cccttgttgc ccgaattggc cagcttgatt 240 atcgcggcca agagtctaatgaataagtaa aacgattgca gt 282 29 71 PRT Conus betulinus 29 Met Met PheLys Leu Gly Val Leu Leu Thr Ile Tyr Met Leu Leu Phe 1 5 10 15 Pro PheThr Ala Leu Pro Leu Asp Gly Asp Gln Pro Ala Asp Gln Pro 20 25 30 Leu GluArg Met Gln Tyr Asp Met Leu Arg Ala Val Asn Pro Trp Phe 35 40 45 Asp ProVal Lys Arg Cys Cys Ser Arg Asn Cys Ala Val Cys Ile Pro 50 55 60 Cys CysPro Asn Trp Pro Ala 65 70 30 18 PRT Conus betulinus PEPTIDE (1)..(18)Xaa at residue 11, 14 and 17 is Pro or Hyp; Xaa at residue 16 is Trp orbromo-Trp 30 Cys Cys Ser Arg Asn Cys Ala Val Cys Ile Xaa Cys Cys Xaa AsnXaa 1 5 10 15 Xaa Ala 31 325 DNA Conus bullatus 31 caagaaggat cgatagcagttcatgatgtc taaactggga gtcttgttga ccatctgtct 60 gcttctgttt cccctttttgctcttccgca ggatggagat caacctgcag accgacctgc 120 agagcgtatg caggacgacatttcatctga gcagaattcc ttgcttgaga agagagttac 180 tgacaggtgc tgcaaagggaagagggaatg cggcagatgg tgcagagatc actcgcgttg 240 ttgcggtcga cgataagctgttgatgacca gctttgttat cacggctaca tcaagtgtct 300 agtgaataag taaaatgattgcagt 325 32 77 PRT Conus bullatus 32 Met Met Ser Lys Leu Gly Val LeuLeu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Pro Leu Phe Ala Leu Pro GlnAsp Gly Asp Gln Pro Ala Asp Arg Pro 20 25 30 Ala Glu Arg Met Gln Asp AspIle Ser Ser Glu Gln Asn Ser Leu Leu 35 40 45 Glu Lys Arg Val Thr Asp ArgCys Cys Lys Gly Lys Arg Glu Cys Gly 50 55 60 Arg Trp Cys Arg Asp His SerArg Cys Cys Gly Arg Arg 65 70 75 33 23 PRT Conus bullatus PEPTIDE(1)..(23) Xaa at residue 11 is Glu or gamma-carboxy Glu; Xaa at residue15 is Trp or bromo-Trp 33 Val Thr Asp Arg Cys Cys Lys Gly Lys Arg XaaCys Gly Arg Xaa Cys 1 5 10 15 Arg Asp His Ser Arg Cys Cys 20 34 326 DNAConus bullatus 34 caagagggat cgatagcagt tcatgatgtc taaactggga gtcttgttgaccatctgtct 60 gcttctgttt cccctttttg ctcttcggca ggatggagat caacctgcagaccgacctgc 120 agagcgtatg caggatgaca tttcatctga gcagaatccc ttgcttgagaagagagttgg 180 tgacaggtgc tgcaaaggga agagggggtg cggcagatgg tgcagagatcactcacgttg 240 ttgcggtcga cgataacgtg ttgatgacca gctttgttat cacggctacatcaagtgtct 300 tagtgattaa gtaaaacgat tgcagt 326 35 77 PRT Conus bullatus35 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 510 15 Pro Leu Phe Ala Leu Arg Gln Asp Gly Asp Gln Pro Ala Asp Arg Pro 2025 30 Ala Glu Arg Met Gln Asp Asp Ile Ser Ser Glu Gln Asn Pro Leu Leu 3540 45 Glu Lys Arg Val Gly Asp Arg Cys Cys Lys Gly Lys Arg Gly Cys Gly 5055 60 Arg Trp Cys Arg Asp His Ser Arg Cys Cys Gly Arg Arg 65 70 75 36 23PRT Conus bullatus PEPTIDE (1)..(23) Xaa at residue 15 is Trp orbromo-Trp 36 Val Gly Asp Arg Cys Cys Lys Gly Lys Arg Gly Cys Gly Arg XaaCys 1 5 10 15 Arg Asp His Ser Arg Cys Cys 20 37 331 DNA Conus bullatus37 caagaaggat cgatagcagt tcatgatgtc taaactggga gtcttgttga ccatctgtct 60gcttctgttt cccctttttg ctcttccgca ggatggagat caacctgcag accgacctgc 120agagcgtatg caggacgaca tttcatctga gcagaatccc ttgcttgaga agagagttgg 180tgaaaggtgc tgcaaaaacg ggaagagggg gtgcggcaga tggtgcagag atcactcacg 240ttgttgcggt cgacgataac gtgttgatga ccgaggcttt cgttatcacg gctacatcaa 300gtgtctagtg aataagtaaa acgattgcag t 331 38 78 PRT Conus bullatus 38 MetMet Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15Pro Leu Phe Ala Leu Pro Gln Asp Gly Asp Gln Pro Ala Asp Arg Pro 20 25 30Ala Glu Arg Met Gln Asp Asp Ile Ser Ser Glu Gln Asn Pro Leu Leu 35 40 45Glu Lys Arg Val Gly Glu Arg Cys Cys Lys Asn Gly Lys Arg Gly Cys 50 55 60Gly Arg Trp Cys Arg Asp His Ser Arg Cys Cys Gly Arg Arg 65 70 75 39 24PRT Conus bullatus PEPTIDE (1)..(24) Xaa at residue 3 is Glu orgamma-carboxy Glu; Xaa at residue 16 is Trp or bromo-Trp 39 Val Gly XaaArg Cys Cys Lys Asn Gly Lys Arg Gly Cys Gly Arg Xaa 1 5 10 15 Cys ArgAsp His Ser Arg Cys Cys 20 40 337 DNA Conus bullatus 40 caagagggatcgatagcagt tcatgatgtc taaactggga gtcttgttga ccatctgtct 60 gcttctgtttcccctttttg ctcttccgca ggacggagat caacctgcag accgacctgc 120 agagcgtatgcaggacgacc tttcatctga gcagcatccc ttgtttgaga agagaattgt 180 tgacaggtgctgcaacaaag ggaacgggaa gagggggtgc agcagatggt gcagagatca 240 ctcacgttgttgcggtcgac gatgaactgt tgatgaccga ggctttggtt atcacggcta 300 catcaagtgtctagtgaata agtaaaacga ttgcagt 337 41 80 PRT Conus bullatus 41 Met MetSer Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 ProLeu Phe Ala Leu Pro Gln Asp Gly Asp Gln Pro Ala Asp Arg Pro 20 25 30 AlaGlu Arg Met Gln Asp Asp Leu Ser Ser Glu Gln His Pro Leu Phe 35 40 45 GluLys Arg Ile Val Asp Arg Cys Cys Asn Lys Gly Asn Gly Lys Arg 50 55 60 GlyCys Ser Arg Trp Cys Arg Asp His Ser Arg Cys Cys Gly Arg Arg 65 70 75 8042 26 PRT Conus bullatus PEPTIDE (1)..(26) Xaa at residue 18 is Trp orbromo-Trp 42 Ile Val Asp Arg Cys Cys Asn Lys Gly Asn Gly Lys Arg Gly CysSer 1 5 10 15 Arg Xaa Cys Arg Asp His Ser Arg Cys Cys 20 25 43 337 DNAConus bullatus 43 caagaaggat cgatagcagt tcatgatgtc taaactggga gtcttgttgaccatctgtct 60 gcttctgttt cccctttttg ctcttccgca ggatggagat caacctgcagaccgacctgc 120 tgagcgtatg caggacgaca tttcatctga gcggaatccc ttgtttgagaagagcgttgg 180 tttatattgc tgccgaccca aacccaacgg gcagatgatg tgcgacagatggtgcgaaaa 240 aaactcacgt tgttgcggtc gacgataatg tgttgatgac cagctttgttatcaaggcta 300 catcaagtat ctagtgaata agtaaaacga ttgcagt 337 44 77 PRTConus bullatus 44 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys LeuLeu Leu Phe 1 5 10 15 Pro Leu Phe Ala Leu Pro Gln Asp Gly Asp Gln ProAla Asp Arg Pro 20 25 30 Ala Glu Arg Met Gln Asp Asp Ile Ser Ser Asn ProLeu Phe Glu Lys 35 40 45 Ser Val Gly Cys Cys Arg Pro Lys Pro Asn Gly GlnMet Met Cys Asp 50 55 60 Arg Trp Cys Glu Lys Asn Ser Arg Cys Cys Gly ArgArg 65 70 75 45 27 PRT Conus bullatus PEPTIDE (1)..(27) Xaa at residue21 is Glu or gamma-carboxy Glu; Xaa at residue 8 and 10 is Pro or Hyp;Xaa at residue 19 is Trp or bromo-Trp; Xaa at residue 4 is Tyr,125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 45Val Gly Leu Xaa Cys Cys Arg Xaa Lys Xaa Asn Gly Gln Met Met Cys 1 5 1015 Asp Arg Xaa Cys Xaa Lys Asn Ser Arg Cys Cys 20 25 46 323 DNA Conusbullatus 46 caagaaggat cgatagcagt tcatgatgtc taaactggga gttttgttgaccatctgtct 60 gcttctgttt ccccttactg ctcttccgat ggatggagat caatctgtagaccgacctgc 120 agaacgtatg caggacgacc tttcatctga gcagcatccc ttgtttgttcagaaaagaag 180 gtgttgcggc gaaggcttga catgccccag atattggaaa aacagtcagatttgtgcttg 240 ttgttaaatg acaacgtgtc gatgaccaac ttcggtatca cgactacgccaagtgtctaa 300 tgaataagta aaacgattgc agt 323 47 74 PRT Conus bullatus 47Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 1015 Pro Leu Thr Ala Leu Pro Met Asp Gly Asp Gln Ser Val Asp Arg Pro 20 2530 Ala Glu Arg Met Gln Asp Asp Leu Ser Ser Glu Gln His Pro Leu Phe 35 4045 Val Gln Lys Arg Arg Cys Cys Gly Glu Gly Leu Thr Cys Pro Arg Tyr 50 5560 Trp Lys Asn Ser Gln Ile Cys Ala Cys Cys 65 70 48 22 PRT Conusbullatus PEPTIDE (1)..(22) Xaa at residue 5 is Glu or gamma-carboxy Glu;Xaa at residue 10 is Pro or Hyp; Xaa at residue 13 is Trp or bromo-Trp;Xaa at residue 12 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr,O-sulpho-Tyr or O-phospho-Tyr 48 Arg Cys Cys Gly Xaa Gly Leu Thr Cys XaaArg Xaa Xaa Lys Asn Ser 1 5 10 15 Gln Ile Cys Ala Cys Cys 20 49 322 DNAConus bullatus 49 caagagggat cgatagcagt tcatgatgtc taaactggga gtcttgttgaccatctgtct 60 gcttctgttt cccctttttg ctcttccgca ggatggagat caacctgcagaccgacctgc 120 tgagcgtatg caggacgaca tttcatctga gcaggatccc ttgtttgttcagaaaagaag 180 gtgttgcggc gaaggcttga catgccccag atattggaaa aacagtcagatttgtgcttg 240 ttgttaaatg acaacgtgtg atgaccaact tcggtatcac gactacgccaagtgtctaat 300 gaataagtaa aacgattgca gt 322 50 74 PRT Conus bullatus 50Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 1015 Pro Leu Phe Ala Leu Pro Gln Asp Gly Asp Gln Pro Ala Asp Arg Pro 20 2530 Ala Glu Arg Met Gln Asp Asp Ile Ser Ser Glu Gln Asp Pro Leu Phe 35 4045 Val Gln Lys Arg Arg Cys Cys Gly Glu Gly Leu Thr Cys Pro Arg Tyr 50 5560 Trp Lys Asn Ser Gln Ile Cys Ala Cys Cys 65 70 51 22 PRT Conusbullatus PEPTIDE (1)..(22) Xaa at residue 5 is Glu or gamma-carboxy Glu;Xaa at residue 10 is Pro or Hyp; Xaa at residue 13 is Trp or bromo-Trp;Xaa at residue 12 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr,O-sulpho-Tyr or O-phospho-Tyr 51 Arg Cys Cys Gly Xaa Gly Leu Thr Cys XaaArg Xaa Xaa Lys Asn Ser 1 5 10 15 Gln Ile Cys Ala Cys Cys 20 52 238 DNAConus capitaneus 52 ggatccatga tgtctaaact gggagtcttg gtgaccatctgcctgcttct gtttcccctt 60 gctgcttttc cactggatgg aaatcaacct gcagaccaccctgcaaagcg tacgcaagat 120 gacagttcag ctgccctgat caatacctgg attgatcattcccattcttg ctgcagggac 180 tgcggtgaag attgtgttgg ttgttgccgg taacgtgttgatgaccaact ttctcgag 238 53 70 PRT Conus capitaneus 53 Gly Ser Met MetSer Lys Leu Gly Val Leu Val Thr Ile Cys Leu Leu 1 5 10 15 Leu Phe ProLeu Ala Ala Phe Pro Leu Asp Gly Asn Gln Pro Ala Asp 20 25 30 His Pro AlaLys Arg Thr Gln Asp Asp Ser Ser Ala Ala Leu Ile Asn 35 40 45 Thr Trp IleAsp His Ser His Ser Cys Cys Arg Asp Cys Gly Glu Asp 50 55 60 Cys Val GlyCys Cys Arg 65 70 54 15 PRT Conus capitaneus PEPTIDE (1)..(15) Xaa atresidue 8 is Glu or gamma-carboxy Glu 54 Ser Cys Cys Arg Asp Cys Gly XaaAsp Cys Val Gly Cys Cys Arg 1 5 10 15 55 323 DNA Conus caracteristicus55 caagagggat cgatagcagt tcatgatgtc taaactggga gtcttgttga ccatctgtct 60gcttctgttt ccccttactg ctcttccaat ggatggagat caacctgcag accaacctgc 120agatcgtatg caggacgaca tttcatctga gcagtatccc ttgtttgata tgagaaaaag 180gtgttgcggc cccggcggtt catgccccgt atatttcaga gacaatttta tttgtggttg 240ttgttaaatg acaacgtgtc gatgaccaac ttcattatca cgactacgcc aagtgtctaa 300tgaataagta aaatgattgc agt 323 56 74 PRT Conus caracteristicus 56 Met MetSer Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 ProLeu Thr Ala Leu Pro Met Asp Gly Asp Gln Pro Ala Asp Gln Pro 20 25 30 AlaAsp Arg Met Gln Asp Asp Ile Ser Ser Glu Gln Tyr Pro Leu Phe 35 40 45 AspMet Arg Lys Arg Cys Cys Gly Pro Gly Gly Ser Cys Pro Val Tyr 50 55 60 PheArg Asp Asn Phe Ile Cys Gly Cys Cys 65 70 57 21 PRT Conuscaracteristicus PEPTIDE (1)..(21) Xaa at residue 4 and 9 is Pro or Hyp;Xaa at residue 11 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr,O-sulpho-Tyr or O-phospho-Tyr 57 Cys Cys Gly Xaa Gly Gly Ser Cys Xaa ValXaa Phe Arg Asp Asn Phe 1 5 10 15 Ile Cys Gly Cys Cys 20 58 316 DNAConus caracteristicus 58 caagagggat cgatagcagt tcatgatgtc taaactgggagtcttgttga ccatctgtct 60 gcttctgttt ccccttactg ctcttccgat ggatggagatgaacctgcaa accgacctgt 120 cgagcgtatg caggacaaca tttcatctga gcagtatcccttgtttgaga agagacgaga 180 ttgttgcact ccgccgaaga aatgcaaaga ccgacaatgcaaaccccaga gatgttgcgc 240 tggacgataa cgtgttgatg accaacttta tcacggctacgtcaagtgtt tagtgaataa 300 gtaaaatgat tgcagt 316 59 75 PRT Conuscaracteristicus 59 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys LeuLeu Leu Phe 1 5 10 15 Pro Leu Thr Ala Leu Pro Met Asp Gly Asp Glu ProAla Asn Arg Pro 20 25 30 Val Glu Arg Met Gln Asp Asn Ile Ser Ser Glu GlnTyr Pro Leu Phe 35 40 45 Glu Lys Arg Arg Asp Cys Cys Thr Pro Pro Lys LysCys Lys Asp Arg 50 55 60 Gln Cys Lys Pro Gln Arg Cys Cys Ala Gly Arg 6570 75 60 22 PRT Conus caracteristicus PEPTIDE (1)..(22) Xaa at residue6, 7 and 17 is Pro or Hyp 60 Arg Asp Cys Cys Thr Xaa Xaa Lys Lys Cys LysAsp Arg Gln Cys Lys 1 5 10 15 Xaa Gln Arg Cys Cys Ala 20 61 314 DNAConus caracteristicus 61 caagagggat cgatagcagt tcatgatgtc taaactgggagtcttgttga ccatctgtct 60 gcttctgttt ccccttactg ctcttccact ggatggagatcaacctgcag atcaatctgc 120 agagcgacct gcagagcgta cgcaggacga cattcagcagcatccgttat atgatccgaa 180 aagaaggtgt tgccgttatc catgccccga cagctgccacggatcttgct gctataagtg 240 ataacatgtt gatggccagc tttgttatca cggccacgtcaagtgtctta atgaataagt 300 aaaacgattg cagt 314 62 72 PRT Conuscaracteristicus 62 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys LeuLeu Leu Phe 1 5 10 15 Pro Leu Thr Ala Leu Pro Leu Asp Gly Asp Gln ProAla Asp Gln Ser 20 25 30 Ala Glu Arg Pro Ala Glu Arg Thr Gln Asp Asp IleGln Gln His Pro 35 40 45 Leu Tyr Asp Pro Lys Arg Arg Cys Cys Arg Tyr ProCys Pro Asp Ser 50 55 60 Cys His Gly Ser Cys Cys Tyr Lys 65 70 63 18 PRTConus caracteristicus PEPTIDE (1)..(18) Xaa at residue 6 and 8 is Pro orHyp; Xaa at residue 5 and 17 is Tyr, 125I-Tyr, mono-iodo-Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 63 Arg Cys Cys Arg Xaa XaaCys Xaa Asp Ser Cys His Gly Ser Cys Cys 1 5 10 15 Xaa Lys 64 292 DNAConus caracteristicus 64 caagagggat cgatagcagt tcatgatgtc taaactgggagccttgttga ccatctgtct 60 acttctgttt tcccttactg ctgttccgct ggatggagatcaacatgcag accaacctgc 120 acagcgtctg caggaccgca ttccaactga agatcatcccttatttgatc ccaacaaacg 180 gtgttgcccg ccggtggcat gcaacatggg atgcaagccttgttgtggat gaccagcttt 240 gttatcgcgg tcttcatgaa gtgtcttaat gaataagtaaaatgattgca gt 292 65 69 PRT Conus caracteristicus 65 Met Met Ser Lys LeuGly Ala Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Ser Leu Thr AlaVal Pro Leu Asp Gly Asp Gln His Ala Asp Gln Pro 20 25 30 Ala Gln Arg LeuGln Asp Arg Ile Pro Thr Glu Asp His Pro Leu Phe 35 40 45 Asp Pro Asn LysArg Cys Cys Pro Pro Val Ala Cys Asn Met Gly Cys 50 55 60 Lys Pro Cys CysGly 65 66 15 PRT Conus caracteristicus PEPTIDE (1)..(15) Xaa at residue3, 4 and 13 is Pro or Hyp 66 Cys Cys Xaa Xaa Val Ala Cys Asn Met Gly CysLys Xaa Cys Cys 1 5 10 15 67 293 DNA Conus caracteristicus 67 caagagggatcgatagcagt tcatgatgtc taaactggga gccttgttga ccatctgtct 60 acttctgttttccctaactg ctgttccgct ggatggagat caacatgcag accaacctgc 120 agagcgtctgcatgaccgcc ttccaactga aaatcatccc ttatatgatc ccgtcaaacg 180 gtgttgcgatgattcggaat gcgactattc ttgctggcct tgctgtatgt ttggataacc 240 tttgttatcgcggcctcatc aagtgtctaa tgaataagta aaacgattgc agt 293 68 71 PRT Conuscaracteristicus 68 Met Met Ser Lys Leu Gly Ala Leu Leu Thr Ile Cys LeuLeu Leu Phe 1 5 10 15 Ser Leu Thr Ala Val Pro Leu Asp Gly Asp Gln HisAla Asp Gln Pro 20 25 30 Ala Glu Arg Leu His Asp Arg Leu Pro Thr Glu AsnHis Pro Leu Tyr 35 40 45 Asp Pro Val Lys Arg Cys Cys Asp Asp Ser Glu CysAsp Tyr Ser Cys 50 55 60 Trp Pro Cys Cys Met Phe Gly 65 70 69 17 PRTConus caracteristicus PEPTIDE (1)..(17) Xaa at residue 6 is Glu orgamma-carboxy Glu; Xaa at residue 13 is Pro or Hyp; Xaa at residue 12 isTrp or bromo-Trp; Xaa at residue 9 is Tyr, 125I-Tyr, mono-iodo-Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 69 Cys Cys Asp Asp Ser XaaCys Asp Xaa Ser Cys Xaa Xaa Cys Cys Met 1 5 10 15 Phe 70 232 DNA Conuscaracteristicus 70 ggatccatga tgtctaaact gggagtcttg ttgaccatctgtctgcttct gtttcccctt 60 actgctgttc cgctggatgg agatcaacct gcagaccgacctgcagagcg taagcaggac 120 gtttcatctg aacagcatcc cttctttgat cccgtcaaacggtgttgccg ccggtgttac 180 atgggatgca tcccttgttg cttttaacgt gttgatgaccaactttctcg ag 232 71 68 PRT Conus caracteristicus 71 Gly Ser Met Met SerLys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu 1 5 10 15 Leu Phe Pro LeuThr Ala Val Pro Leu Asp Gly Asp Gln Pro Ala Asp 20 25 30 Arg Pro Ala GluArg Lys Gln Asp Val Ser Ser Glu Gln His Pro Phe 35 40 45 Phe Asp Pro ValLys Arg Cys Cys Arg Arg Cys Tyr Met Gly Cys Ile 50 55 60 Pro Cys Cys Phe65 72 14 PRT Conus caracteristicus PEPTIDE (1)..(14) Xaa at residue 11is Pro or Hyp; Xaa at residue 6 is Tyr, 125I-Tyr, mono-iodo-Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 72 Cys Cys Arg Arg Cys XaaMet Gly Cys Ile Xaa Cys Cys Phe 1 5 10 73 323 DNA Conus circumcisus 73caagaaggat cgatagcagt tcatgatgtc taaactgggg gtattgttga ccatctgtct 60gcttctgttt ccccttactg ctcttccaat ggatggagat caacctgcag accaacctgc 120agatcgtatg caggacgaca tttcatctga gcagtatccc ttgtttgata agagacgaaa 180gtgttgcggc aaagacgggc catgccccaa atatttcaaa gacaatttta tttgtggttg 240ttgttaaatg acaacgtgtc gatgaccaac ttcgttatca cgattcgcca agtgtcttaa 300tgaataagta aaatgattgc agt 323 74 74 PRT Conus circumcisus 74 Met Met SerLys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Pro LeuThr Ala Leu Pro Met Asp Gly Asp Gln Pro Ala Asp Gln Pro 20 25 30 Ala AspArg Met Gln Asp Asp Ile Ser Ser Glu Gln Tyr Pro Leu Phe 35 40 45 Asp LysArg Arg Lys Cys Cys Gly Lys Asp Gly Pro Cys Pro Lys Tyr 50 55 60 Phe LysAsp Asn Phe Ile Cys Gly Cys Cys 65 70 75 23 PRT Conus circumcisusPEPTIDE (1)..(23) Xaa at residue 9 and 11 is Pro or Hyp; Xaa at residue13 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho-Tyr 75 Arg Lys Cys Cys Gly Lys Asp Gly Xaa Cys Xaa Lys Xaa PheLys Asp 1 5 10 15 Asn Phe Ile Cys Gly Cys Cys 20 76 293 DNA Conus dalli76 caagagggat cgatagcagt tcatgatgtc taaactggga gccttgttga ccatctgtct 60acttctgttt tccctaactg ctgttccgct ggatggagat caacatgcag accaacctgc 120agagcgtctg caggaccgcc ttccaactga aaatcatccc ttatatgatc ccgtcaaacg 180gtgttgcgat gattcggaat gcgactattc ttgctggcct tgctgtattt tatcataacc 240tttgttatcg cggcctcatc aagtgtcaaa tgaataagta aaatgattgc agt 293 77 71 PRTConus dalli 77 Met Met Ser Lys Leu Gly Ala Leu Leu Thr Ile Cys Leu LeuLeu Phe 1 5 10 15 Ser Leu Thr Ala Val Pro Leu Asp Gly Asp Gln His AlaAsp Gln Pro 20 25 30 Ala Glu Arg Leu Gln Asp Arg Leu Pro Thr Glu Asn HisPro Leu Tyr 35 40 45 Asp Pro Val Lys Arg Cys Cys Asp Asp Ser Glu Cys AspTyr Ser Cys 50 55 60 Trp Pro Cys Cys Ile Leu Ser 65 70 78 18 PRT Conusdalli PEPTIDE (1)..(18) Xaa at residue 6 is Glu or gamma-carboxy Glu;Xaa at residue 13 is Pro or Hyp; Xaa at residue 12 is Trp or bromo-Trp;Xaa at residue 9 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr,O-sulpho-Tyr or O-phospho-Tyr 78 Cys Cys Asp Asp Ser Xaa Cys Asp Xaa SerCys Xaa Xaa Cys Cys Ile 1 5 10 15 Leu Ser 79 299 DNA Conus dalli 79caagagggat cgatagcagt tcatgatgtc taaactggga gtcttgttga ccatttgtct 60acttctgttt ccccttactg ctgttccact ggatggagat cagcctgcag accgacctgc 120agagcgtatg caggacggca tttcatctga acatcatcca ttttttgatt ccgtcaaaaa 180gaaacaacag tgttgcccgc cggtggcatg caacatggga tgcgagcctt gttgtggatg 240accagctttg ttatcgcggc tcatgaagtg tcctaatgaa taagtaaaac gattgcagt 299 8072 PRT Conus dalli 80 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile CysLeu Leu Leu Phe 1 5 10 15 Pro Leu Thr Ala Val Pro Leu Asp Gly Asp GlnPro Ala Asp Arg Pro 20 25 30 Ala Glu Arg Met Gln Asp Gly Ile Ser Ser GluHis His Pro Phe Phe 35 40 45 Asp Ser Val Lys Lys Lys Gln Gln Cys Cys ProPro Val Ala Cys Asn 50 55 60 Met Gly Cys Glu Pro Cys Cys Gly 65 70 81 17PRT Conus dalli PEPTIDE (1)..(17) Xaa at residue 1 is Gln or pyro-Glu;Xaa at residue 14 is Glu or gamma-carboxy Glu; Xaa at residue 5, 6 and15is Pro or Hyp 81 Xaa Gln Cys Cys Xaa Xaa Val Ala Cys Asn Met Gly CysXaa Xaa Cys 1 5 10 15 Cys 82 290 DNA Conus dalli 82 caagaaggatcgatagcagt tcatgatgtc taaactggga gtcttgttga tcatatgtct 60 atttctgtttccccttactg ctgttcagct caatggagat cagcctgcag accaatctgc 120 agagcgtatgcaggacaaaa tttcatctga acatcatccc ttttttgatc ccgtcaaacg 180 ttgttgcaacgcggggtttt gccgcttcgg atgcacgcct tgttgttggt gaccagcttt 240 gttatcgcggcctcatcaag tgtctaatga ataagtaaaa tgattgcagt 290 83 69 PRT Conus dalli 83Met Met Ser Lys Leu Gly Val Leu Leu Ile Ile Cys Leu Phe Leu Phe 1 5 1015 Pro Leu Thr Ala Val Gln Leu Asn Gly Asp Gln Pro Ala Asp Gln Ser 20 2530 Ala Glu Arg Met Gln Asp Lys Ile Ser Ser Glu His His Pro Phe Phe 35 4045 Asp Pro Val Lys Arg Cys Cys Asn Ala Gly Phe Cys Arg Phe Gly Cys 50 5560 Thr Pro Cys Cys Trp 65 84 16 PRT Conus dalli PEPTIDE (1)..(16) Xaa atresidue 13 is Pro or Hyp; Xaa at residue 16 is Trp or bromo-Trp 84 CysCys Asn Ala Gly Phe Cys Arg Phe Gly Cys Thr Xaa Cys Cys Xaa 1 5 10 15 85288 DNA Conus distans 85 caagagggat cgatagcagt tcatgatgtc taaactgggagtcttgctga ccatctttct 60 gcttctgttt ccccttactg ctgttccgct ggatggagatcaacccgcag acggacttgc 120 agagcgcatg caggacgaca gttcagctgc actgattagagactggcttc ttcaaacccg 180 acagtgttgt gtgcatccat gcccatgcac gccttgctgtagatgaccag ctttgtcatc 240 gcggctacgt caagtatcta atgaataagt aagtaaaacgattgcagt 288 86 67 PRT Conus distans 86 Met Met Ser Lys Leu Gly Val LeuLeu Thr Ile Phe Leu Leu Leu Phe 1 5 10 15 Pro Leu Thr Ala Val Pro LeuAsp Gly Asp Gln Pro Ala Asp Gly Leu 20 25 30 Ala Glu Arg Met Gln Asp AspSer Ser Ala Ala Leu Ile Arg Asp Trp 35 40 45 Leu Leu Gln Thr Arg Gln CysCys Val His Pro Cys Pro Cys Thr Pro 50 55 60 Cys Cys Arg 65 87 14 PRTConus distans PEPTIDE (1)..(14) Xaa at residue 1 is Gln or pyro-Glu; Xaaat residue 6, 8 and 11 is Pro or Hyp 87 Xaa Cys Cys Val His Xaa Cys XaaCys Thr Xaa Cys Cys Arg 1 5 10 88 303 DNA Conus ermineus 88 acctcaagagggatcgatcg cagttcatga tgtctaaact gggagccttg ttgaccatct 60 gtctgcttctgtttcccatt actgctcttc tgatggatgg agatcagcct gcagaccgac 120 ctgcagagcgtacggaggat gacatttcat ctgactacat tccctgttgc agttggccat 180 gcccccgatactccaacggt aaacttgttt gtttttgttg ccttggatga taatgtgttg 240 atgaccaactttgttatcac ggctacgtca agtgtctact gaataagtaa aatgattgca 300 gta 303 89 67PRT Conus ermineus 89 Met Met Ser Lys Leu Gly Ala Leu Leu Thr Ile CysLeu Leu Leu Phe 1 5 10 15 Pro Ile Thr Ala Leu Leu Met Asp Gly Asp GlnPro Ala Asp Arg Pro 20 25 30 Ala Glu Arg Thr Glu Asp Asp Ile Ser Ser AspTyr Ile Pro Cys Cys 35 40 45 Ser Trp Pro Cys Pro Arg Tyr Ser Asn Gly LysLeu Val Cys Phe Cys 50 55 60 Cys Leu Gly 65 90 20 PRT Conus ermineusPEPTIDE (1)..(20) Xaa at residue 5 and 7 is Pro or Hyp; Xaa at residue 4is Trp or bromo-Trp; Xaa at residue 9 is Tyr, 125I-Tyr, mono-iodo-Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 90 Cys Cys Ser Xaa Xaa CysXaa Arg Xaa Ser Asn Gly Lys Leu Val Cys 1 5 10 15 Phe Cys Cys Leu 20 91241 DNA Conus generalis 91 ggatccatga tgtctaaact gggagtcttg ttgaccatctgtctggttct gtttcccctt 60 actgctcttc cactggatgg agaacaacct gtagaccgacatgccgagca tatgcaggat 120 gacaattcag ctgcacagaa cccctgggtt attgccatcagacagtgttg cacgttctgc 180 aactttggat gccaaccttg ttgcctcacc tgataacgtgttgatgacca actttctcga 240 g 241 92 70 PRT Conus generalis 92 Gly Ser MetMet Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Val 1 5 10 15 Leu PhePro Leu Thr Ala Leu Pro Leu Asp Gly Glu Gln Pro Val Asp 20 25 30 Arg HisAla Glu His Met Gln Asp Asp Asn Ser Ala Ala Gln Asn Pro 35 40 45 Trp ValIle Ala Ile Arg Gln Cys Cys Thr Phe Cys Asn Phe Gly Cys 50 55 60 Gln ProCys Cys Leu Thr 65 70 93 16 PRT Conus generalis PEPTIDE (1)..(16) Xaa atresidue 1 is Gln or pyro-Glu; Xaa at residue 12 is Pro or Hyp 93 Xaa CysCys Thr Phe Cys Asn Phe Gly Cys Gln Xaa Cys Cys Leu Thr 1 5 10 15 94 241DNA Conus generalis 94 ggatccatga tgtctaaact gggagtcttg ttgaccatctgtctggttct gtttcccctt 60 actgctcttc cactggatgg agaacaacct gtagaccgacatgccgagca tatgcaggat 120 gacaattcag ctgcacagaa cccctgggtt attgccatcagacagtgttg cacgttctgc 180 aactttggat gccagccttg ttgcgtcccc tgataacgtgttgatgacca actttctcga 240 g 241 95 70 PRT Conus generalis 95 Gly Ser MetMet Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Val 1 5 10 15 Leu PhePro Leu Thr Ala Leu Pro Leu Asp Gly Glu Gln Pro Val Asp 20 25 30 Arg HisAla Glu His Met Gln Asp Asp Asn Ser Ala Ala Gln Asn Pro 35 40 45 Trp ValIle Ala Ile Arg Gln Cys Cys Thr Phe Cys Asn Phe Gly Cys 50 55 60 Gln ProCys Cys Val Pro 65 70 96 16 PRT Conus generalis PEPTIDE (1)..(16) Xaa atresidue 1 is Gln or pyro-Glu; Xaa at residue 12 and 16 is Pro or Hyp 96Xaa Cys Cys Thr Phe Cys Asn Phe Gly Cys Gln Xaa Cys Cys Val Xaa 1 5 1015 97 862 DNA Conus geographus 97 gtcgactcta gaggatccga caacaaagagtcaaccccac tgccacgtca agagcgaagc 60 gccacagcta agacaagagg gatcgatagcagttcatgat gtctaaactg ggagtcttgt 120 tgaccatctg tctgcttctg tttccccttactgctcttcc gatggatgga gatgaacctg 180 caaaccgacc tgtcgagcgt atgcaggacaacatttcatc tgagcagtat cccttgtttg 240 agaagagacg agattgttgc actccgccgaagaaatgcaa agaccgacaa tgcaaacccc 300 agagatgttg cgctggacga taacgtgttgatgaccaact ttatcacggc tacgtcaagt 360 gtttagtgaa taagtaaaat gattgcagtcttgctcagat ttgcttttgt gttttggtct 420 aaagatcaat gaccaaaccg ttgttttgatgcggattgtc atatatttct cgattccaat 480 ccaacactag atgatttaat cacgatagattaattttcta tcaatgcctt gatttttcgt 540 ctgtcatatc agttttgttt atatttattttttcgtcact gtctacacaa acgcatgcat 600 gcacgcatgc acgcacacac gcacgcacgctcgcacaaac atgcgcgcgc acgcacacac 660 acacacacac acacaaacac acacacaagcaatcacacaa ttattgacat tatttattta 720 ttcattgatg tatttgttat tcgtttgcttgtttttagaa tagtttgagg ccgtcttttt 780 ggatttattt gaactgcttt attgtatacgagtacttcgt gctttgaaac actgctgaaa 840 ataaaacaaa cactgacgta gc 862 98 75PRT Conus geographus 98 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile CysLeu Leu Leu Phe 1 5 10 15 Pro Leu Thr Ala Leu Pro Met Asp Gly Asp GluPro Ala Asn Arg Pro 20 25 30 Val Glu Arg Met Gln Asp Asn Ile Ser Ser GluGln Tyr Pro Leu Phe 35 40 45 Glu Lys Arg Arg Asp Cys Cys Thr Pro Pro LysLys Cys Lys Asp Arg 50 55 60 Gln Cys Lys Pro Gln Arg Cys Cys Ala Gly Arg65 70 75 99 22 PRT Conus geographus PEPTIDE (1)..(22) Xaa at residue 6,7 and 17 is Pro or Hyp 99 Arg Asp Cys Cys Thr Xaa Xaa Lys Lys Cys LysAsp Arg Gln Cys Lys 1 5 10 15 Xaa Gln Arg Cys Cys Ala 20 100 860 DNAConus geographus 100 ggccagacga caacaaagag tcaaccccac tgccacgtcaagagcgaagc gccacagcta 60 agacaagagg gatcgatagc agttcatgat gtctaaactgggagtcttgt tgaccatctg 120 tctgcttctg tttcccctta ctgctcttcc gatggatggagatgaacctg caaaccgacc 180 tgtcgagcgt atgcaggaca acatttcatc tgagcagtatcccttgtttg agaagagacg 240 agattgttgc actccgccga ggaaatgcaa agaccgacgatgcaaaccca tgaaatgttg 300 cgctggacga taacgtgttg atgaccaact ttatcacggctagctcagtg tttagtgaat 360 aagtaaaatg attgcagtct tgctcagatt gcttttgtgttttggtctaa gatcaatgac 420 caaaccgttg ttttgatgcg gattgtcata tatttctcgattccaatcca acactagatg 480 atttaatcac gatagattaa ttttctatca atgccttgatttttcgtctg tcatatcagt 540 tttgtttata tttatttttt cgtcactgtc tacacaaacgcatgcatgca cgcatgcacg 600 cacacacgca cgcacgctcg cacaaacatg cgcgcgcacgcacacacaca cacacacaca 660 aacacacaca cgaagcaatc acacaattag ttgacattatttatttattc attgatgtat 720 ttgttattcg tttgcttgtt tttagaatag tttgaggccgtctttttgga tttatttgaa 780 ctgctttatt gtatacgagt acttcgtgct ttgaaacactgctgaaaata aaacaaacac 840 tgacgtagca aaaaaaaaaa 860 101 75 PRT Conusgeographus 101 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu LeuLeu Phe 1 5 10 15 Pro Leu Thr Ala Leu Pro Met Asp Gly Asp Glu Pro AlaAsn Arg Pro 20 25 30 Val Glu Arg Met Gln Asp Asn Ile Ser Ser Glu Gln TyrPro Leu Phe 35 40 45 Glu Lys Arg Arg Asp Cys Cys Thr Pro Pro Arg Lys CysLys Asp Arg 50 55 60 Arg Cys Lys Pro Met Lys Cys Cys Ala Gly Arg 65 7075 102 22 PRT Conus geographus PEPTIDE (1)..(22) Xaa at residue 6, 7 and17 is Pro or Hyp 102 Arg Asp Cys Cys Thr Xaa Xaa Arg Lys Cys Lys Asp ArgArg Cys Lys 1 5 10 15 Xaa Met Lys Cys Cys Ala 20 103 22 PRT Conusgeographus PEPTIDE (1)..(22) Xaa at residue 6, 7 and 17 is Pro or Hyp103 Arg Asp Cys Cys Thr Xaa Xaa Lys Lys Cys Lys Asp Arg Arg Cys Lys 1 510 15 Xaa Leu Lys Cys Cys Ala 20 104 321 DNA Conus gloriamaris 104ctcactatag gaattcgagc tcggtacacg ggatcgatag cagttcatga tgtctaaact 60gggagccttg ttgaccatct gtctacttct gttttcccta actgctgttc cgctggatgg 120agatcaacat gcagaccaac ctgcagagcg tctgcatgac cgccttccaa ctgaaaatca 180tcccttatat gatcccgtca aacggtgttg cgatgattcg gaatgcgact attcttgctg 240gccttgctgt atgtttggat aacctttgtt atcgcggcct cgataagtgt ctaatgaata 300agtaaaacga ttgcagtagg c 321 105 71 PRT Conus gloriamaris 105 Met Met SerLys Leu Gly Ala Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Ser LeuThr Ala Val Pro Leu Asp Gly Asp Gln His Ala Asp Gln Pro 20 25 30 Ala GluArg Leu His Asp Arg Leu Pro Thr Glu Asn His Pro Leu Tyr 35 40 45 Asp ProVal Lys Arg Cys Cys Asp Asp Ser Glu Cys Asp Tyr Ser Cys 50 55 60 Trp ProCys Cys Met Phe Gly 65 70 106 17 PRT Conus gloriamaris PEPTIDE (1)..(17)Xaa at residue is 6 Glu or gamma-carboxy Glu; Xaa at residue 13 is Proor Hyp; Xaa at residue 12 is Trp or bromo-Trp; Xaa at residue 9 is Tyr,125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 106Cys Cys Asp Asp Ser Xaa Cys Asp Xaa Ser Cys Xaa Xaa Cys Cys Met 1 5 1015 Phe 107 257 DNA Conus gloriamaris 107 gttcatgatg tctaaactgggagtcttgtt gatcatctgt ctacttctgt ttccccttac 60 tgctgttccg ctggatggagatcaacctgc agaccgatat gcagagcgta tgcaggacga 120 catttcatct gaacatcatcccatgtttga tgccgtcaga gggtgttgcc atctgttggc 180 atgccgcttc ggatgctcgccttgttgttg gtgatcagct ttgttatcgc ggcctcatca 240 agtgactcta atgcaaa 257108 69 PRT Conus gloriamaris 108 Met Met Ser Lys Leu Gly Val Leu Leu IleIle Cys Leu Leu Leu Phe 1 5 10 15 Pro Leu Thr Ala Val Pro Leu Asp GlyAsp Gln Pro Ala Asp Arg Tyr 20 25 30 Ala Glu Arg Met Gln Asp Asp Ile SerSer Glu His His Pro Met Phe 35 40 45 Asp Ala Val Arg Gly Cys Cys His LeuLeu Ala Cys Arg Phe Gly Cys 50 55 60 Ser Pro Cys Cys Trp 65 109 17 PRTConus gloriamaris PEPTIDE (1)..(17) Xaa at residue 14 is Pro or Hyp; Xaaat residue 17 is Trp or bromo-Trp 109 Gly Cys Cys His Leu Leu Ala CysArg Phe Gly Cys Ser Xaa Cys Cys 1 5 10 15 Xaa 110 471 DNA Conusgloriamaris 110 gagacgacaa ggaacagtca accccacagc cacgccaaga gcagacagccacagctacgt 60 gaagaagggt ggagagaggt tcgtgatgtt gaaaatggga gtggtgctattcatcttcct 120 ggtactgttt cccctggcaa cgctccagct ggatgcagat caacctgtagaacgatatgc 180 ggagaacaaa cagctcctca acccagatga aaggagggaa atcatattgcatgctctggg 240 gacgcgatgc tgttcttggg atgtgtgcga ccacccgagt tgtacttgctgcggcggtta 300 gcgccgaaca tccatggcgc tgtgctgggc ggttttatcc aacaacgacagcgtttgttg 360 atttcatgta tcattgcgcc cacgtctctt gtctaagaat gacgaacatgattgcactct 420 ggttcagatt tcgtgttctt ttctgacaat aaatgacaaa actccaaaaa a471 111 71 PRT Conus gloriamaris 111 Met Leu Lys Met Gly Val Val Leu PheIle Phe Leu Val Leu Phe Pro 1 5 10 15 Leu Ala Thr Leu Gln Leu Asp AlaAsp Gln Pro Val Glu Arg Tyr Ala 20 25 30 Glu Asn Lys Gln Leu Leu Asn ProAsp Glu Arg Arg Glu Ile Ile Leu 35 40 45 His Ala Leu Gly Thr Arg Cys CysSer Trp Asp Val Cys Asp His Pro 50 55 60 Ser Cys Thr Cys Cys Gly Gly 6570 112 16 PRT Conus gloriamaris PEPTIDE (1)..(16) Xaa at residue 10 isPro or Hyp; Xaa at residue 4 is Trp or bromo-Trp 112 Cys Cys Ser Xaa AspVal Cys Asp His Xaa Ser Cys Thr Cys Cys Gly 1 5 10 15 113 304 DNA Conuslaterculatus 113 cgacctcaag aaggatcgat agcagttcat gatgtctaaa ctgggagtcttgttgaccat 60 ctgtctgctt ctgtttcccc ttactgctct tccgatggat ggagatcaacctgcagaccg 120 acctgcagag cgtatgcagg acgtttcatc tgaacagcat cccttgtatgatcccgtcaa 180 acggtgttgc gactggccat gcagcggatg catcccttgt tgctaatagtaacaacgtgt 240 tgataaccaa ctttcttacc acgactacgt caagtgtcta atgaataagtaaaatgattg 300 cagt 304 114 65 PRT Conus laterculatus 114 Met Met SerLys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Pro LeuThr Ala Leu Pro Met Asp Gly Asp Gln Pro Ala Asp Arg Pro 20 25 30 Ala GluArg Met Gln Asp Val Ser Ser Glu Gln His Pro Leu Tyr Asp 35 40 45 Pro ValLys Arg Cys Cys Asp Trp Pro Cys Ser Gly Cys Ile Pro Cys 50 55 60 Cys 65115 13 PRT Conus laterculatus PEPTIDE (1)..(13) Xaa at residue 5 and 11is Pro or Hyp; Xaa at residue 4 is Trp or bromo-Trp 115 Cys Cys Asp XaaXaa Cys Ser Gly Cys Ile Xaa Cys Cys 1 5 10 116 313 DNA Conuslaterculatus 116 cgacctcaag aaggatcgat agcagttcat gatgtctaaa ctgggagtcttgttgaccat 60 ctgtctgctt ctgtttcccc ttactgctct ggatggagat caacctgcagaccgacttgc 120 agagcgtatg caggacgaca tttcatctga gcagcatccc tttgaaaagagacgagactg 180 ttgcacacct ccgaagaaat gcagagaccg acaatgcaaa cctgcacgttgttgcggagg 240 ataacgtgtt gatgaccaac tttgttatca cggctacgtc aagtgtctagtgaataagta 300 aaacgattgc agt 313 117 71 PRT Conus laterculatus 117 MetMet Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15Pro Leu Thr Ala Leu Asp Gly Asp Gln Pro Ala Asp Arg Leu Ala Glu 20 25 30Arg Met Gln Asp Asp Ile Ser Ser Glu Gln His Pro Phe Glu Lys Arg 35 40 45Arg Asp Cys Cys Thr Pro Pro Lys Lys Cys Arg Asp Arg Gln Cys Lys 50 55 60Pro Ala Arg Cys Cys Gly Gly 65 70 118 22 PRT Conus laterculatus PEPTIDE(1)..(22) Xaa at residue 6, 17 and 17 is Pro or Hyp 118 Arg Asp Cys CysThr Xaa Xaa Lys Lys Cys Arg Asp Arg Gln Cys Lys 1 5 10 15 Xaa Ala ArgCys Cys Gly 20 119 314 DNA Conus laterculatus 119 gggatcgata gcagttcatgatgtctaaac tgggagtctt gttgaccatc tgtctgcttc 60 tgtttcccct tactgctcttccgatggatg gagatcaact tgcacgccga tctgcagagc 120 gtatgcagga caacatttcatctgagcagc atcacctctt tgaaaagaga cgaccaccat 180 gttgcaccta tgacgggagttgcctaaaag aatcatgcat gcgtaaagct tgttgcggat 240 gataacgtgt tgatgaccaactttgttatc acggctactc aagtgtctaa tgaataagta 300 aaatgattgc agta 314 12074 PRT Conus laterculatus 120 Met Met Ser Lys Leu Gly Val Leu Leu ThrIle Cys Leu Leu Leu Phe 1 5 10 15 Pro Leu Thr Ala Leu Pro Met Asp GlyAsp Gln Leu Ala Arg Arg Ser 20 25 30 Ala Glu Arg Met Gln Asp Asn Ile SerSer Glu Gln His His Leu Phe 35 40 45 Glu Lys Arg Arg Pro Pro Cys Cys ThrTyr Asp Gly Ser Cys Leu Lys 50 55 60 Glu Ser Cys Met Arg Lys Ala Cys CysGly 65 70 121 22 PRT Conus laterculatus PEPTIDE (1)..(22) Xaa at residue14 is Glu or gamma-carboxy Glu; Xaa at residue 2 and 3 is Pro or Hyp;Xaa at residue 7 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr,O-sulpho-Tyr or O-phospho- Tyr 121 Arg Xaa Xaa Cys Cys Thr Xaa Asp GlySer Cys Leu Lys Xaa Ser Cys 1 5 10 15 Met Arg Lys Ala Cys Cys 20 122 314DNA Conus laterculatus 122 gggatcgata gcagttcatg atgtctaaac tgggagtcttgttgaccacc tgtctgcttc 60 tgtttcccct tactgctctt ccgatggatg gagatcaacttgcacgccga cctgcagagc 120 gtatgcagga caacatttca tctgagcagc atcccttctttgaaaggaga cgaccaccat 180 gttgcaccta tgacgggagt tgcctaaaag aatcatgcaagcgtaaagct tgttgcggat 240 aataacgtgt tgatgaccaa ctttgttatc acggctactcaagtgtctaa tgaataagta 300 aaatgattgc agta 314 123 74 PRT Conuslaterculatus 123 Met Met Ser Lys Leu Gly Val Leu Leu Thr Thr Cys Leu LeuLeu Phe 1 5 10 15 Pro Leu Thr Ala Leu Pro Met Asp Gly Asp Gln Leu AlaArg Arg Pro 20 25 30 Ala Glu Arg Met Gln Asp Asn Ile Ser Ser Glu Gln HisPro Phe Phe 35 40 45 Glu Arg Arg Arg Pro Pro Cys Cys Thr Tyr Asp Gly SerCys Leu Lys 50 55 60 Glu Ser Cys Lys Arg Lys Ala Cys Cys Gly 65 70 12422 PRT Conus laterculatus PEPTIDE (1)..(22) Xaa at residue 14 is Glu orgamma-carboxy Glu; Xaa at residue 2 and 3 is Pro or Hyp; Xaa at residue7 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho- Tyr 124 Arg Xaa Xaa Cys Cys Thr Xaa Asp Gly Ser Cys Leu LysXaa Ser Cys 1 5 10 15 Lys Arg Lys Ala Cys Cys 20 125 247 DNA Conusleopardus 125 ggatccatga tgtctaaact gggagtcttg ttgaccgtct gtctgcttctgtttcccctt 60 actgctcttc ggctggttgg agatcaacct gcagagcgac ctgcaaagcgtacgcaggac 120 gacattccag atggacagca tccgttaaat gataggcaga taaactgttgcccgtggcca 180 tgccctagta catgccgcca tcaatgctgc cattaatgat aacgtgttgatgaccaactt 240 tctcgag 247 126 71 PRT Conus leopardus 126 Gly Ser MetMet Ser Lys Leu Gly Val Leu Leu Thr Val Cys Leu Leu 1 5 10 15 Leu PhePro Leu Thr Ala Leu Arg Leu Val Gly Asp Gln Pro Ala Glu 20 25 30 Arg ProAla Lys Arg Thr Gln Asp Asp Ile Pro Asp Gly Gln His Pro 35 40 45 Leu AsnAsp Arg Gln Ile Asn Cys Cys Pro Trp Pro Cys Pro Ser Thr 50 55 60 Cys ArgHis Gln Cys Cys His 65 70 127 19 PRT Conus leopardus PEPTIDE (1)..(19)Xaa at residue 1 is Gln or pyro-Glu; Xaa at residue 6, 8 and 10 is Proor Hyp; Xaa at residue 7 is Trp or bromo-Trp 127 Xaa Ile Asn Cys Cys XaaXaa Xaa Cys Xaa Ser Thr Cys Arg His Gln 1 5 10 15 Cys Cys His 128 244DNA Conus lividus 128 ggatccatga tgtctaaact gggagtcttg ttgaccgtctgtctgcttct gtttcccctt 60 actgctcttc ggctggttag agatcaacct gcagagcgacctgcaaagcg tacgcaggac 120 gacattccaa atggacagga tccgttaatt gataggcagataaattgttg cccttggcca 180 tgccctgatt catgccacta tcaatgctgc cactgataacgtgttgatga ccaactttct 240 cgag 244 129 71 PRT Conus lividus 129 Gly SerMet Met Ser Lys Leu Gly Val Leu Leu Thr Val Cys Leu Leu 1 5 10 15 LeuPhe Pro Leu Thr Ala Leu Arg Leu Val Arg Asp Gln Pro Ala Glu 20 25 30 ArgPro Ala Lys Arg Thr Gln Asp Asp Ile Pro Asn Gly Gln Asp Pro 35 40 45 LeuIle Asp Arg Gln Ile Asn Cys Cys Pro Trp Pro Cys Pro Asp Ser 50 55 60 CysHis Tyr Gln Cys Cys His 65 70 130 19 PRT Conus lividus PEPTIDE (1)..(19)Xaa at residue 1 is Gln or pyro-Glu; Xaa at residue 6, 8 and 10 is Proor Hyp; Xaa at residue 7 is Trp or bromo-Trp; Xaa at residue 15 is Tyr,125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 130Xaa Ile Asn Cys Cys Xaa Xaa Xaa Cys Xaa Asp Ser Cys His Xaa Gln 1 5 1015 Cys Cys His 131 275 DNA Conus lynceus 131 aaggatcgat agcagttcatgatgtctaaa ctgggagtct tgttgaccat ctgtctgctt 60 ctgtttcccc ttactgctcttccgatggat ggagatcaat ctgcagaccg acttgcagag 120 cgtatgcagg acaacatttcatctgagcag catcccttct ttgaaaagag aggacgagac 180 tgttgcacac ctccgaggaaatgcagagac cgagcctgca aacctcaacg ttgttgcgga 240 ggataagctg ttgatgaccaactttgttat acggc 275 132 75 PRT Conus lynceus 132 Met Met Ser Lys LeuGly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Pro Leu Thr AlaLeu Pro Met Asp Gly Asp Gln Ser Ala Asp Arg Leu 20 25 30 Ala Glu Arg MetGln Asp Asn Ile Ser Ser Glu Gln His Pro Phe Phe 35 40 45 Glu Lys Arg GlyArg Asp Cys Cys Thr Pro Pro Arg Lys Cys Arg Asp 50 55 60 Arg Ala Cys LysPro Gln Arg Cys Cys Gly Gly 65 70 75 133 23 PRT Conus lynceus PEPTIDE(1)..(23) Xaa at residue 7, 8 and 18 is Pro or Hyp 133 Gly Arg Asp CysCys Thr Xaa Xaa Arg Lys Cys Arg Asp Arg Ala Cys 1 5 10 15 Lys Xaa GlnArg Cys Cys Gly 20 134 803 DNA Conus magus 134 caagagggat cgatagcagttcatgatgtc taaactggga gtcttgttga ccatctgtct 60 gcttctgttt ccccttactgctcttccgat ggatggagat gaacctgcaa accgacctgt 120 cgagcgtatg caggacaacatttcatctga gcagtatccc ttgtttgaga agagacgaga 180 ttgttgcact ccgccgaagaaatgcaaaga ccgacaatgc aaaccccaga gatgttgcgc 240 tggacgataa cgtgttgatgaccaacttta tcacggctac gtcaagtgtt tagtgaataa 300 gtaaaatgat tgcagtcttgctcagatttg cttttgtgtt ttggtctaaa gatcaatgac 360 caaaccgttg ttttgatgcggattgtcata tatttctcga ttccaatcca acactagatg 420 atttaatcac gatagattaattttctatca atgccttgat ttttcgtctg tcatatcagt 480 tttgtttata tttattttttcgtcactgtc tacacaaacg catgcatgca cgcatgcacg 540 cacacacgca cgcacgctcgcacaaacatg cgcgcgcacg cacacacaca cacacacaca 600 caaacacaca cacgaagcaatcacacaatt agttgacatt atttatttat tcattgatgt 660 atttgttatt cgtttgcttgtttttagaat agtttgaggc cgtctttttg gatttatttg 720 aactgcttta ttgtatacgagtacttcgtg cggggaaaca ctgctgaaaa taaaacaaac 780 actgacgtag caaaaaaaaaaaa 803 135 75 PRT Conus magus 135 Met Met Ser Lys Leu Gly Val Leu LeuThr Ile Cys Leu Leu Leu Phe 1 5 10 15 Pro Leu Thr Ala Leu Pro Met AspGly Asp Glu Pro Ala Asn Arg Pro 20 25 30 Val Glu Arg Met Gln Asp Asn IleSer Ser Glu Gln Tyr Pro Leu Phe 35 40 45 Glu Lys Arg Arg Asp Cys Cys ThrPro Pro Lys Lys Cys Lys Asp Arg 50 55 60 Gln Cys Lys Pro Gln Arg Cys CysAla Gly Arg 65 70 75 136 22 PRT Conus magus PEPTIDE (1)..(22) Xaa atresidue 6 and 7 is Pro or Hyp 136 Arg Asp Cys Cys Thr Xaa Xaa Lys LysCys Lys Asp Arg Gln Cys Lys 1 5 10 15 Xaa Gln Arg Cys Cys Ala 20 137 656DNA Conus magus 137 caagagggat cgatagcagt tcatgatgtc taaactgggagtcttgttga ccatctgtct 60 gcttctgttt ccccttactg ctcttccaat ggatggagatcaacctgcag accaacctgc 120 agatcgtatg caggacgaca tttcatctga gcagtatcccttgtttgata tgagaaaaag 180 gtgttgcggc cccggcggtt catgccccgt atatttcagagacaatttta tttgtggttg 240 ttgttaaatg acaacgtgtc gatgaccaac ttcattatcacgactacgcc aagtgtctaa 300 tgaataaata aaatgattgc agtctcgctc agatttgcttttgtattttg gtctaaagat 360 caatgaccaa accgttgttt tggtgtggat tttcatatatttctcgagtc ctatccaaca 420 ctagatgatt taatcacgat agatctgatt tttttatcaaaggcttggtt tttcgtctgt 480 cacatcagtt ttgtttatat ttaatttttc gtcactgattacacacacgc atgaacgcac 540 agagtactaa cacatacaca cacacacaca cacacacacacacacacaca cacacacaca 600 cacacacaca cacgcgcgcg cgcggcgcca tctagtagcgccgcgacgac acacac 656 138 74 PRT Conus magus 138 Met Met Ser Lys Leu GlyVal Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Pro Leu Thr Ala LeuPro Met Asp Gly Asp Gln Pro Ala Asp Gln Pro 20 25 30 Ala Asp Arg Met GlnAsp Asp Ile Ser Ser Glu Gln Tyr Pro Leu Phe 35 40 45 Asp Met Arg Lys ArgCys Cys Gly Pro Gly Gly Ser Cys Pro Val Tyr 50 55 60 Phe Arg Asp Asn PheIle Cys Gly Cys Cys 65 70 139 21 PRT Conus magus PEPTIDE (1)..(21) Xaaat residue 4 and 9 is Pro or Hyp; Xaa at residue is 11 Tyr, 125I-Tyr,mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 139 Cys CysGly Xaa Gly Gly Ser Cys Xaa Val Xaa Phe Arg Asp Asn Phe 1 5 10 15 IleCys Gly Cys Cys 20 140 594 DNA Conus magus 140 caagagggat cgatagcagttcatgatgtc taaactggga gtcttgttga ccatctgttt 60 gcttctgttt ccccttactgctcttccgag ggatggagat caatctgtag accgacctgc 120 agagcgtatg caggacgacatttcatctga gctgcatccc ttgtcaatca gaaaaagaat 180 gtgttgcggc gagagtgcgccatgccccag ctatttcaga aacagtcaga tttgtcattg 240 ttgttaaatg acaacgtgtcgatgaccacc ttcgttatca cgactaatga taagtaaaat 300 gattgcagtc tcgctcagatttgcttttgt attttggtct aaagatcaat gaccaaaccg 360 ttgttttgat gtggattttcatatatttct cgagtcctat ccaacactag atgatttaat 420 cacgatagat ctgatttttttatcaaagcc ttggtttttc gtctgtcaca tcagttttgt 480 ttatatttaa tttttcgtcactgattacac acacgcatga acgcacagac gtactaacac 540 atacacacac acacacacacacacacacac acacacacac acacacacac acac 594 141 74 PRT Conus magus 141 MetMet Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15Pro Leu Thr Ala Leu Pro Arg Asp Gly Asp Gln Ser Val Asp Arg Pro 20 25 30Ala Glu Arg Met Gln Asp Asp Ile Ser Ser Glu Leu His Pro Leu Ser 35 40 45Ile Arg Lys Arg Met Cys Cys Gly Glu Ser Ala Pro Cys Pro Ser Tyr 50 55 60Phe Arg Asn Ser Gln Ile Cys His Cys Cys 65 70 142 22 PRT Conus magusPEPTIDE (1)..(22) Xaa at residue 5 is Glu or gamma-carboxy Glu; Xaa atresidue 8 and 10 is Pro or Hyp; Xaa at residue 12 is Tyr, 125I-Tyr,mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 142 Met CysCys Gly Xaa Ser Ala Xaa Cys Xaa Ser Xaa Phe Arg Asn Ser 1 5 10 15 GlnIle Cys His Cys Cys 20 143 501 DNA Conus magus 143 caagagggat cgatagcagttcatgatgtc taaactggga gtcttgttga ccatctgtct 60 gcttctgttt ccccttactgctcttccaat ggatggagat caacctgcag accaacctgc 120 agatcgtatg caggacgacatttcatctga gcagtatccc ttgtttgata agagacaaaa 180 gtgttgcggc cccggcggttcatgccccgt atatttcaca gacaatttta tttgtggttg 240 ttgttaaatg acaacgtgtcgatgaccaac ttcattatca cgactacgcc aagtgtctaa 300 tgaataaata aaatgattgcagtctcgctc agatttgctt ttgtatttgg tctaaagatc 360 aatgaccaaa ccgttgttttggtgctggat tttcatatat ttctcgattc ctatccaaca 420 ctagatgatt taatcacgatagatctgatt tttttatcaa tgccttaatt ttttgctctg 480 tcatatcagt tttgtttata t501 144 74 PRT Conus magus 144 Met Met Ser Lys Leu Gly Val Leu Leu ThrIle Cys Leu Leu Leu Phe 1 5 10 15 Pro Leu Thr Ala Leu Pro Met Asp GlyAsp Gln Pro Ala Asp Gln Pro 20 25 30 Ala Asp Arg Met Gln Asp Asp Ile SerSer Glu Gln Tyr Pro Leu Phe 35 40 45 Asp Lys Arg Gln Lys Cys Cys Gly ProGly Gly Ser Cys Pro Val Tyr 50 55 60 Phe Thr Asp Asn Phe Ile Cys Gly CysCys 65 70 145 23 PRT Conus magus PEPTIDE (1)..(23) Xaa at residue 1 isGln or pyro-Glu; Xaa at residue 6 and 11 is Pro or Hyp; Xaa at residue13 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho-Tyr 145 Xaa Lys Cys Cys Gly Xaa Gly Gly Ser Cys Xaa Val XaaPhe Thr Asp 1 5 10 15 Asn Phe Ile Cys Gly Cys Cys 20 146 454 DNA Conusmagus 146 caagagggat cgatagcagt tcatgatgtc taaactggga gtcttgttgaccatctgtct 60 gcttctgttt ccccttactg ctcttccaat ggatggagat caacctgcagaccaacctgc 120 agatcgtatg caggacgaca tttcatctga gcagtatccc ttgtttgataagagacaaaa 180 gtgttgcggc cccggcggtt catgccccgt atatttcaga gacaattttatttgtggttg 240 ttgttaaatg acaacgtgtc gatgaccatc ttcattatca cgactacgccaagtgtctaa 300 tgaataaata aaatgattgc agtctcgctc agatttgctt ttgtattttggtctaaagat 360 caatgaccaa accgttgttt tggtgtggat tttcatatat ttctcgattcctatccaaca 420 ctagatgatt taatcacgat agatctgatt tttt 454 147 74 PRTConus magus 147 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu LeuLeu Phe 1 5 10 15 Pro Leu Thr Ala Leu Pro Met Asp Gly Asp Gln Pro AlaAsp Gln Pro 20 25 30 Ala Asp Arg Met Gln Asp Asp Ile Ser Ser Glu Gln TyrPro Leu Phe 35 40 45 Asp Lys Arg Gln Lys Cys Cys Gly Pro Gly Gly Ser CysPro Val Tyr 50 55 60 Phe Arg Asp Asn Phe Ile Cys Gly Cys Cys 65 70 14823 PRT Conus magus PEPTIDE (1)..(23) Xaa at residue 1 is Gln orpyro-Glu; Xaa at residue 6 and 11 is Pro or Hyp; Xaa at residue 13 isTyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr148 Xaa Lys Cys Cys Gly Xaa Gly Gly Ser Cys Xaa Val Xaa Phe Arg Asp 1 510 15 Asn Phe Ile Cys Gly Cys Cys 20 149 22 PRT Conus magus PEPTIDE(1)..(22) Xaa at residue 1 is Gln or pyro-Glu; Xaa at residue 10 and 20is Pro or Hyp; Xaa at residue 12 is Tyr, 125I-Tyr, mono-iodo-Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 149 Xaa Lys Cys Cys Ser GlyGly Ser Cys Xaa Leu Xaa Phe Arg Asp Arg 1 5 10 15 Leu Ile Cys Xaa CysCys 20 150 19 PRT Conus marmoreus PEPTIDE (1)..(19) Xaa at residue 16 isPro or Hyp 150 Ser Lys Gln Cys Cys His Leu Ala Ala Cys Arg Phe Gly CysThr Xaa 1 5 10 15 Cys Cys Asn 151 321 DNA Conus marmoreus 151 caagaaggatcgatagcagt tcatgatgtc taaactggga gtcttgttga ccatctgtct 60 gcttctgtttcccgttactg ctcttccgat ggatggtgat caacctgcag accgacttgt 120 agagcgtatgcaggacaaca tttcatctga gcagcatccc ttctttgaaa agagaagagg 180 aggctgttgcacacctccga ggaaatgcaa agaccgagcc tgcaaacctg cacgttgctg 240 cggcccaggataacgtgttg atgaccaact ttgttatcac ggctacgtca agtgtctagt 300 gaataagtaaaacgattgca g 321 152 76 PRT Conus marmoreus 152 Met Met Ser Lys Leu GlyVal Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Pro Val Thr Ala LeuPro Met Asp Gly Asp Gln Pro Ala Asp Arg Leu 20 25 30 Val Glu Arg Met GlnAsp Asn Ile Ser Ser Glu Gln His Pro Phe Phe 35 40 45 Glu Lys Arg Arg GlyGly Cys Cys Thr Pro Pro Arg Lys Cys Lys Asp 50 55 60 Arg Ala Cys Lys ProAla Arg Cys Cys Gly Pro Gly 65 70 75 153 24 PRT Conus marmoreus PEPTIDE(1)..(24) Xaa at residue 3, 8, 18 and 24 is Pro or Hyp 153 Arg Gly GlyCys Cys Thr Xaa Xaa Arg Lys Cys Lys Asp Arg Ala Cys 1 5 10 15 Lys XaaAla Arg Cys Cys Gly Xaa 20 154 296 DNA Conus marmoreus 154 gagctcggtaccccgacctc aagagggatc gatagcagtt catgatgtct aaactgggaa 60 tcttgttgaccatctgtcta cttctatttc cccttactgc tgttccgctg gatggagatc 120 aacctgcagaccgacctgca gagcgtatgc aggacgacat ttcatctgaa catcatccct 180 tttttgatcccgtcaaacgg tgttgcaggt tatcatgcgg cctgggatgc cacccttgtt 240 gtggatgaccagctttgtta tcgcggcctc atcaagtgtc taatgaataa gtaaaa 296 155 68 PRT Conusmarmoreus 155 Met Met Ser Lys Leu Gly Ile Leu Leu Thr Ile Cys Leu LeuLeu Phe 1 5 10 15 Pro Leu Thr Ala Val Pro Leu Asp Gly Asp Gln Pro AlaAsp Arg Pro 20 25 30 Ala Glu Arg Met Gln Asp Asp Ile Ser Ser Glu His HisPro Phe Phe 35 40 45 Asp Pro Val Lys Arg Cys Cys Arg Leu Ser Cys Gly LeuGly Cys His 50 55 60 Pro Cys Cys Gly 65 156 14 PRT Conus marmoreusPEPTIDE (1)..(14) Xaa at residue 12 is Pro or Hyp 156 Cys Cys Arg LeuSer Cys Gly Leu Gly Cys His Xaa Cys Cys 1 5 10 157 355 DNA Conusmarmoreus 157 ggcctacacc aagcttgcat gcctgcaggt cgactctaga ggatccccgatcgatagcag 60 ttcatgatgt ctagactggg agtcttgttg accatctgtc tacttctgtttccccttact 120 gctgttccgc tggatggaga tcaacctgcg gaccgacctg cagagcgcctgcaggacgac 180 atttcatctg aacatcatcc ccattttgat tccggcagag agtgttgcggttcgttcgca 240 tgccgctttg gatgcgtgcc ttgttgtgta tgaccagctt tgttatcacggcctcatcga 300 gtgtctaatg aataagtaaa acgattgcag taggcgggta ccgagctcgaattcc 355 158 69 PRT Conus marmoreus 158 Met Met Ser Arg Leu Gly Val LeuLeu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Pro Leu Thr Ala Val Pro LeuAsp Gly Asp Gln Pro Ala Asp Arg Pro 20 25 30 Ala Glu Arg Leu Gln Asp AspIle Ser Ser Glu His His Pro His Phe 35 40 45 Asp Ser Gly Arg Glu Cys CysGly Ser Phe Ala Cys Arg Phe Gly Cys 50 55 60 Val Pro Cys Cys Val 65 15917 PRT Conus marmoreus PEPTIDE (1)..(17) Xaa at residue 1 is Glu orgamma-carboxy Glu; Xaa at residue 14 is Pro or Hyp 159 Xaa Cys Cys GlySer Phe Ala Cys Arg Phe Gly Cys Val Xaa Cys Cys 1 5 10 15 Val 160 295DNA Conus marmoreus 160 cgacctcaag agggatcgat agcagttcat gatgtctaaactgggagtct tgttgaccat 60 ctgtctactt ctatttcccc ttactgctgt tccgctggatggagaccaac ctgcagaccg 120 acctgcagag cgtatgcagg acgacatttc atctgaacgtcatccttttt ttgatcgcag 180 caaacagtgt tgccatctgc cggcatgccg cttcggatgtacgccttgtt gttggtgatc 240 agctttgtta tcgcgtcctc atcaagtgtc taatgaataagtaaaatgat tgcag 295 161 67 PRT Conus marmoreus 161 Met Met Ser Lys LeuGly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Pro Leu Thr AlaVal Pro Leu Asp Gly Asp Gln Pro Ala Asp Arg Pro 20 25 30 Ala Glu Arg MetGln Asp Asp Ile Ser Ser His Pro Phe Phe Asp Arg 35 40 45 Ser Lys Gln CysCys His Leu Pro Ala Cys Arg Phe Gly Cys Thr Pro 50 55 60 Cys Cys Trp 65162 19 PRT Conus marmoreus PEPTIDE (1)..(19) Xaa at residue 8 and 16 isPro or Hyp; Xaa at residue 19 is Trp or bromo-Trp 162 Ser Lys Gln CysCys His Leu Xaa Ala Cys Arg Phe Gly Cys Thr Xaa 1 5 10 15 Cys Cys Xaa163 235 DNA Conus marmoreus 163 ggatccatga tgtctaaact gggagtcttgttgaccatct gtctgcttct gtttcccctt 60 actgctcttc cgctggatgg agatcaacctgcagaccaac gtgcagagcg tacgcaggcc 120 gagaagcatt ccttgcctga tccgagaatgggctgttgcc cgtttccatg caaaaccagt 180 tgcactactt tgtgttgcgg gtgatgataacgtgttgatg accaactttc tcgag 235 164 67 PRT Conus marmoreus 164 Gly SerMet Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu 1 5 10 15 LeuPhe Pro Leu Thr Ala Leu Pro Leu Asp Gly Asp Gln Pro Ala Asp 20 25 30 GlnArg Ala Glu Arg Thr Gln Ala Glu Lys His Ser Leu Pro Asp Pro 35 40 45 ArgMet Gly Cys Cys Pro Phe Pro Cys Lys Thr Ser Cys Thr Thr Leu 50 55 60 CysCys Gly 65 165 17 PRT Conus marmoreus PEPTIDE (1)..(17) Xaa at residue 5and 7 is Pro or Hyp 165 Met Gly Cys Cys Xaa Phe Xaa Cys Lys Thr Ser CysThr Thr Leu Cys 1 5 10 15 Cys 166 16 PRT Conus marmoreus PEPTIDE(1)..(16) Xaa at residue 4 and 6 is Trp or bromo-Trp 166 Cys Cys His XaaAsn Xaa Cys Asp His Leu Cys Ser Cys Cys Gly Ser 1 5 10 15 167 357 DNAConus marmoreus 167 gccaagcttg catgcctgca ggatgactct agaggatccccacctcaaga gggatcgata 60 gcagttcatg atgtctaaac tgggagtctt gttgaccatctgtctacttc tgtttgccct 120 tactgctgtt ccgctggatg gagatcaacc tgcagaccgacctgcagaac gtatgcagga 180 cgacatttca tctgaacgtc atcccatgtt tgatgccgtcagagattgtt gcccgttgcc 240 ggcatgcccc tttggatgca acccttgttg tggatgaccagctttgttat cgggacctca 300 tcaagtgtct aatgaataag taaaaaacga ttcgagtgggtaccgagctc gaattcc 357 168 67 PRT Conus marmoreus 168 Met Met Ser LysLeu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Ala Leu ThrAla Val Pro Leu Asp Gly Asp Gln Pro Ala Asp Arg Pro 20 25 30 Ala Glu ArgMet Gln Asp Asp Ile Ser Ser His Pro Met Phe Asp Ala 35 40 45 Val Arg AspCys Cys Pro Leu Pro Ala Cys Pro Phe Gly Cys Asn Pro 50 55 60 Cys Cys Gly65 169 16 PRT Conus marmoreus PEPTIDE (1)..(16) Xaa at residue 4, 6, 9and 14 is Pro or Hyp 169 Asp Cys Cys Xaa Leu Xaa Ala Cys Xaa Phe Gly CysAsn Xaa Cys Cys 1 5 10 15 170 16 PRT Conus marmoreus PEPTIDE (1)..(16)Xaa at residue 4 and 13 is Pro or Hyp 170 Cys Cys Ala Xaa Ser Ala CysArg Leu Gly Cys Arg Xaa Cys Cys Arg 1 5 10 15 171 16 PRT Conus marmoreusPEPTIDE (1)..(16) Xaa at residue 4 and 13 is Pro or Hyp 171 Cys Cys AlaXaa Ser Ala Cys Arg Leu Gly Cys Arg Xaa Cys Cys Arg 1 5 10 15 172 16 PRTConus marmoreus PEPTIDE (1)..(16) Xaa at residue 4 and 13 is Pro or Hyp172 Cys Cys Ala Xaa Ser Ala Cys Arg Leu Gly Cys Arg Xaa Cys Cys Arg 1 510 15 173 17 PRT Conus marmoreus PEPTIDE (1)..(17) Xaa at residue 14 isPro or Hyp 173 Gly Cys Cys Gly Ser Phe Ala Cys Arg Phe Gly Cys Val XaaCys Cys 1 5 10 15 Val 174 244 DNA Conus nobilis 174 ggatccatgatgtctaaact gggagtcttg ttgaccatct gtctacttct gtttcccctt 60 actgctcttccgctggatga agatcaaccg gtacaccgac ctgcagagcg tatgcaggac 120 atttcatctgatcaacatct cttctttgat ctcatcaaac ggtgctgcga gttgccatgc 180 gggccaggcttttgcgtccc ttgttgctga catcaataac gtgttgatga ccaactttct 240 cgag 244 17569 PRT Conus nobilis 175 Gly Ser Met Met Ser Lys Leu Gly Val Leu Leu ThrIle Cys Leu Leu 1 5 10 15 Leu Phe Pro Leu Thr Ala Leu Pro Leu Asp GluAsp Gln Pro Val His 20 25 30 Arg Pro Ala Glu Arg Met Gln Asp Ile Ser SerAsp Gln His Leu Phe 35 40 45 Phe Asp Leu Ile Lys Arg Cys Cys Glu Leu ProCys Gly Pro Gly Phe 50 55 60 Cys Val Pro Cys Cys 65 176 15 PRT Conusnobilis PEPTIDE (1)..(15) Xaa at residue 3 is Glu or gamma-carboxy Glu;Xaa at residue 5, 8 adn 13 is Pro or Hyp 176 Cys Cys Xaa Leu Xaa Cys GlyXaa Gly Phe Cys Val Xaa Cys Cys 1 5 10 15 177 262 DNA Conus nobilis 177ggatccatga tgtctaaact gggagtcttg ttgaccatct gtctacttct gtttcccctt 60actgcttttc cgatggatgg agatcaacct gcagaccaac ctgcagatcg tatgcaggac 120gacatttcat ctgagcagta tcccttgttt gataagagac aaaagtgttg cactgggaag 180aaggggtcat gctccggcaa agcatgcaaa aatctcaaat gttgctctgg acgataacgt 240gttgatgacc aactttctcg ag 262 178 78 PRT Conus nobilis 178 Gly Ser MetMet Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu 1 5 10 15 Leu PhePro Leu Thr Ala Phe Pro Met Asp Gly Asp Gln Pro Ala Asp 20 25 30 Gln ProAla Asp Arg Met Gln Asp Asp Ile Ser Ser Glu Gln Tyr Pro 35 40 45 Leu PheAsp Lys Arg Gln Lys Cys Cys Thr Gly Lys Lys Gly Ser Cys 50 55 60 Ser GlyLys Ala Cys Lys Asn Leu Lys Cys Cys Ser Gly Arg 65 70 75 179 23 PRTConus nobilis PEPTIDE (1)..(23) Xaa at residue 1 is Gln or pyro-Glu 179Xaa Lys Cys Cys Thr Gly Lys Lys Gly Ser Cys Ser Gly Lys Ala Cys 1 5 1015 Lys Asn Leu Lys Cys Cys Ser 20 180 238 DNA Conus pulicarius 180ggatccatga tgtctaaact gggagttttg ttgaccatct gtctgcttct gtttcccctt 60actgctgttc cgctggatgg agatcaacct gcagaccgac ctgcagagcg tatgcaggac 120attgcaactg aacagcatcc cttctttgat cccgtcaaac ggtgttgcaa cagctgttac 180atgggatgca tcccttgttg cttctagtaa taacgtgttg atgaccaact ttctcgag 238 18168 PRT Conus pulicarius 181 Gly Ser Met Met Ser Lys Leu Gly Val Leu LeuThr Ile Cys Leu Leu 1 5 10 15 Leu Phe Pro Leu Thr Ala Val Pro Leu AspGly Asp Gln Pro Ala Asp 20 25 30 Arg Pro Ala Glu Arg Met Gln Asp Ile AlaThr Glu Gln His Pro Phe 35 40 45 Phe Asp Pro Val Lys Arg Cys Cys Asn SerCys Tyr Met Gly Cys Ile 50 55 60 Pro Cys Cys Phe 65 182 14 PRT Conuspulicarius PEPTIDE (1)..(14) Xaa at residue 11 is Pro or Hyp; Xaa atresidue 5 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho-Tyr 182 Cys Cys Asn Ser Cys Xaa Met Gly Cys Ile Xaa Cys CysPhe 1 5 10 183 238 DNA Conus quercinus 183 ggatccatga tgtctaaactgggagtcttg ttgaccatct gtctgcttct gtttcccctt 60 acagctcttc agctggatggagatcaacct gcagaccgac ctgcagagcg tacgcaggac 120 attgcatctg aacagtatcgaaagtttgat cagagacaga ggtgttgcca gtggccatgc 180 cccggtagtt gcagatgctgccgtactggt taacgtgttg atgaccaact ttctcgag 238 184 70 PRT Conus quercinus184 Gly Ser Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu 1 510 15 Leu Phe Pro Leu Thr Ala Leu Gln Leu Asp Gly Asp Gln Pro Ala Asp 2025 30 Arg Pro Ala Glu Arg Thr Gln Asp Ile Ala Ser Glu Gln Tyr Arg Lys 3540 45 Phe Asp Gln Arg Gln Arg Cys Cys Gln Trp Pro Cys Pro Gly Ser Cys 5055 60 Arg Cys Cys Arg Thr Gly 65 70 185 17 PRT Conus quercinus PEPTIDE(1)..(17) Xaa at residue 1 is Gln or pyro-Glu; Xaa at residue 7 and 9 isPro or Hyp; Xaa at residue 6 is Trp or bromo-Trp 185 Xaa Arg Cys Cys GlnXaa Xaa Cys Xaa Gly Ser Cys Arg Cys Cys Arg 1 5 10 15 Thr 186 15 PRTConus quercinus PEPTIDE (1)..(15) Xaa at residue 11 and 14 is Pro or Hyp186 Cys Cys Ser Gln Asp Cys Leu Val Cys Ile Xaa Cys Cys Xaa Asn 1 5 1015 187 15 PRT Conus quercinus PEPTIDE (1)..(15) Xaa at residue 11 14 isPro or Hyp; Xaa at residue 7 is Trp or bromo-Trp 187 Cys Cys Ser Arg HisCys Xaa Val Cys Ile Xaa Cys Cys Xaa Asn 1 5 10 15 188 323 DNA Conusradiatus 188 tcaagaagga tcgatagcag ttcatgatgt ctaaactggg agtcttgttgaccatctgtc 60 tgcttctgtt tccccttact gctcttccga tggatggaga tcaacctgtagaccgacttg 120 cagagcgtat gcaggacaac atttcatctg agcagcatac cttctttgaaaagagactac 180 catcgtgttg ctcccttaac ttgcggcttt gcccagtacc agcatgcaaacgtaaccctt 240 gttgcacagg ataacgtgtt gatgaccaac tttgttatca cggctacgtcaagtgtctag 300 tgaataagta aaacgattgc agt 323 189 76 PRT Conus radiatus189 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 510 15 Pro Leu Thr Ala Leu Pro Met Asp Gly Asp Gln Pro Val Asp Arg Leu 2025 30 Ala Glu Arg Met Gln Asp Asn Ile Ser Ser Glu Gln His Thr Phe Phe 3540 45 Glu Lys Arg Leu Pro Ser Cys Cys Ser Leu Asn Leu Arg Leu Cys Pro 5055 60 Val Pro Ala Cys Lys Arg Asn Pro Cys Cys Thr Gly 65 70 75 190 24PRT Conus radiatus PEPTIDE (1)..(24) Xaa at residue 2, 13, 15 and 21 isPro or Hyp 190 Leu Xaa Ser Cys Cys Ser Leu Asn Leu Arg Leu Cys Xaa ValXaa Ala 1 5 10 15 Cys Lys Arg Asn Xaa Cys Cys Thr 20 191 336 DNA Conusradiatus 191 aggtcgactc tagaggatcc ccaaggatcg atagcagttc atgatgtctaaactgggagt 60 cttgttgacc atctgtctgc ttctgtttcc ccttactgct cttccgatggatggagatca 120 acctgcagac cgacttgcag agcgtatgca ggacgacatt tcatctgagcagcatccctt 180 ctttaaaaag agacaacaaa gatgttgcac cgttaagagg atttgtccagtaccagcatg 240 cagaagtaaa ccttgttgca aatcataacg tattgatgac caactttgttatcacggcta 300 cgtcaagtgt ctagtgaata agtaaaatga ttgcag 336 192 75 PRTConus radiatus 192 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys LeuLeu Leu Phe 1 5 10 15 Pro Leu Thr Ala Leu Pro Met Asp Gly Asp Gln ProAla Asp Arg Leu 20 25 30 Ala Glu Arg Met Gln Asp Asp Ile Ser Ser Glu GlnHis Pro Phe Phe 35 40 45 Lys Lys Arg Gln Gln Arg Cys Cys Thr Val Lys ArgIle Cys Pro Val 50 55 60 Pro Ala Cys Arg Ser Lys Pro Cys Cys Lys Ser 6570 75 193 24 PRT Conus radiatus PEPTIDE (1)..(24) Xaa at residue 1 isGln or pyro-Glu; Xaa at residue 12, 14 and 20 is Pro or Hyp 193 Xaa GlnArg Cys Cys Thr Val Lys Arg Ile Cys Xaa Val Xaa Ala Cys 1 5 10 15 ArgSer Lys Xaa Cys Cys Lys Ser 20 194 326 DNA Conus radiatus 194 acctcaagaaggatcgatag cagttcatga tgtctaaact gggagtcttg ttgaccatct 60 gtctgcttctgtttcccgtt actgctcttc cgatggatgg tgatcaacct gcagaccgac 120 ttgtagagcgtatgcaggac aacatttcat ctgagcagca tcccttcttt gaaaagagaa 180 gaggaggctgttgcacacct ccgaggaaat gcaaagaccg agcctgcaaa cctgcacgtt 240 gctgcggcccaggataacgt gttgatgacc aactttgtta tcacggctac gtcaagtgtc 300 tagtgaataagtaaaacgat tgcagt 326 195 76 PRT Conus radiatus 195 Met Met Ser Lys LeuGly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Pro Val Thr AlaLeu Pro Met Asp Gly Asp Gln Pro Ala Asp Arg Leu 20 25 30 Val Glu Arg MetGln Asp Asn Ile Ser Ser Glu Gln His Pro Phe Phe 35 40 45 Glu Lys Arg ArgGly Gly Cys Cys Thr Pro Pro Arg Lys Cys Lys Asp 50 55 60 Arg Ala Cys LysPro Ala Arg Cys Cys Gly Pro Gly 65 70 75 196 24 PRT Conus radiatusPEPTIDE (1)..(24) Xaa at residue 7, 8, 18 and 24 is Pro or Hyp 196 ArgGly Gly Cys Cys Thr Xaa Xaa Arg Lys Cys Lys Asp Arg Ala Cys 1 5 10 15Lys Xaa Ala Arg Cys Cys Gly Xaa 20 197 238 DNA Conus rattus 197ggatccatga tgtctaaact gggagtcttg gtgaccatct gcctgcttct gttccctctt 60gctgcttttc cactggatgg agatcaacct gcagaccacc ctgcaaagcg tacgcaagat 120gacagttcag ctgccctgat caatgcctgg cttgatgaat cccagacttg ctgcagtaac 180tgcggtgaag attgtgatgg ttgttgccag taacgtgttg atgaccaact ttctcgag 238 19870 PRT Conus rattus 198 Gly Ser Met Met Ser Lys Leu Gly Val Leu Val ThrIle Cys Leu Leu 1 5 10 15 Leu Phe Pro Leu Ala Ala Phe Pro Leu Asp GlyAsp Gln Pro Ala Asp 20 25 30 His Pro Ala Lys Arg Thr Gln Asp Asp Ser SerAla Ala Leu Ile Asn 35 40 45 Ala Trp Leu Asp Glu Ser Gln Thr Cys Cys SerAsn Cys Gly Glu Asp 50 55 60 Cys Asp Gly Cys Cys Gln 65 70 199 16 PRTConus rattus PEPTIDE (1)..(16) Xaa at residue 1 is Gln or pyro-Glu; Xaaat residue 9 is Glu or gamma-carboxy Glu 199 Xaa Thr Cys Cys Ser Asn CysGly Xaa Asp Cys Asp Gly Cys Cys Gln 1 5 10 15 200 327 DNA Conusstercusmuscarum 200 gacctcaaga gggatcgata gcagttcgtg atgtctaaactgggagtctt gttgaccatc 60 tgtctgcttc tgtttcctct tactgctctt ccgatggatggagatcaacc tgcagaccaa 120 cctgcagatc gtatgcagga cgacatttca tctgagcagtatcccttgtt tgataagaga 180 caaaagtgtt gcactgggaa gaaggggtca tgctccggcaaagcatgcaa aaatctcaaa 240 tgttgctctg gacgataacg tgttgatgac caactttgttatcacggcta cgtcaagtgt 300 ctaatgaata agtaaaacga ttgcagt 327 201 75 PRTConus stercusmuscarum 201 Met Ser Lys Leu Gly Val Leu Leu Thr Ile CysLeu Leu Leu Phe Pro 1 5 10 15 Leu Thr Ala Leu Pro Met Asp Gly Asp GlnPro Ala Asp Gln Pro Ala 20 25 30 Asp Arg Met Gln Asp Asp Ile Ser Ser GluGln Tyr Pro Leu Phe Asp 35 40 45 Lys Arg Gln Lys Cys Cys Thr Gly Lys LysGly Ser Cys Ser Gly Lys 50 55 60 Ala Cys Lys Asn Leu Lys Cys Cys Ser GlyArg 65 70 75 202 23 PRT Conus stercusmuscarum PEPTIDE (1)..(23) Xaa atresidue 1 is Gln or pyro-Glu 202 Xaa Lys Cys Cys Thr Gly Lys Lys Gly SerCys Ser Gly Lys Ala Cys 1 5 10 15 Lys Asn Leu Lys Cys Cys Ser 20 203 316DNA Conus stercusmuscarum 203 gatcgatagc agttcgtgat gtctaaactgggagtcttgt tgaccatctg tctgcttctg 60 tttcccctta ctgctcttcc gatggatggagatcaacctg cagaccaacc tgcagatcgt 120 atgcagaacg acatttcatc tgagcagtatcccttgtttg ataagagaca aaagtgttgc 180 ggccccggcg cgtcatgccc cagatatttcaaagacaatt ttatttgtgg ttgttgttaa 240 atgacaacgt gtcgatgacc aacttcgttatcacgacttc gccaagtgtc taatgaataa 300 gtaaaacgat tgcagt 316 204 73 PRTConus stercusmuscarum 204 Met Ser Lys Leu Gly Val Leu Leu Thr Ile CysLeu Leu Leu Phe Pro 1 5 10 15 Leu Thr Ala Leu Pro Met Asp Gly Asp GlnPro Ala Asp Gln Pro Ala 20 25 30 Asp Arg Met Gln Asn Asp Ile Ser Ser GluGln Tyr Pro Leu Phe Asp 35 40 45 Lys Arg Gln Lys Cys Cys Gly Pro Gly AlaSer Cys Pro Arg Tyr Phe 50 55 60 Lys Asp Asn Phe Ile Cys Gly Cys Cys 6570 205 23 PRT Conus stercusmuscarum PEPTIDE (1)..(23) Xaa at residue 1is Gln or pyro-Glu; Xaa at residue 6 and 11 is Pro or Hyp; Xaa atresidue 13 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho- Tyr 205 Xaa Lys Cys Cys Gly Xaa Gly Ala Ser Cys Xaa Arg XaaPhe Lys Asp 1 5 10 15 Asn Phe Ile Cys Gly Cys Cys 20 206 331 DNA Conusstriatus 206 cgacctttca agagggatcg atagcagttc gcgatgtcta aactgggggtattgttgacc 60 atctgtctgc ttctgtttcc ccttactgct cttccgatgg atgaagatcaacctgcagac 120 caacttgaag atcgtatgca ggacgacatt tcatctgagc agtatccctcgtttgttagg 180 agacaaaagt gttgcggcga aggctcgtca tgccccaaat atttcaaaaacaattttatt 240 tgtggttgtt gttaaatgac aacgtgtcga tgaccaactt cgttatcacgactacgccaa 300 gtgtcttgtc taatgataat aaaatgattc c 331 207 73 PRT Conusstriatus 207 Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu PhePro 1 5 10 15 Leu Thr Ala Leu Pro Met Asp Glu Asp Gln Pro Ala Asp GlnLeu Glu 20 25 30 Asp Arg Met Gln Asp Asp Ile Ser Ser Glu Gln Tyr Pro SerPhe Val 35 40 45 Arg Arg Gln Lys Cys Cys Gly Glu Gly Ser Ser Cys Pro LysTyr Phe 50 55 60 Lys Asn Asn Phe Ile Cys Gly Cys Cys 65 70 208 23 PRTConus striatus PEPTIDE (1)..(23) Xaa at residue 1 is Gln or pyro-Glu;Xaa at residue 6 is Glu or gamma-carboxy Glu; Xaa at residue 11 is Proor Hyp; Xaa at residue 13 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr,O-sulpho-Tyr or O-phospho-Tyr 208 Xaa Lys Cys Cys Gly Xaa Gly Ser SerCys Xaa Lys Xaa Phe Lys Asn 1 5 10 15 Asn Phe Ile Cys Gly Cys Cys 20 209256 DNA Conus striatus 209 ggatccatga tgtctaaact gggagtcttg ttgaccgtctgtctgcttct gtttcccctt 60 actgctcttc cgctggatgg agatcaacct gcagaccgacctgcagagcg tatgcaggac 120 gacatttcat ctgacgagca tcccttgttt gataagagacaaaactgttg caatggggga 180 tgctccagca aatggtgcag agatcacgca cgttgttgcggtcgatgata acgtgttgat 240 gaccaacttt ctcgag 256 210 75 PRT Conusstriatus 210 Gly Ser Met Met Ser Lys Leu Gly Val Leu Leu Thr Val Cys LeuLeu 1 5 10 15 Leu Phe Pro Leu Thr Ala Leu Pro Leu Asp Gly Asp Gln ProAla Asp 20 25 30 Arg Pro Ala Glu Arg Met Gln Asp Asp Ile Ser Ser Asp GluHis Pro 35 40 45 Leu Phe Asp Lys Arg Gln Asn Cys Cys Asn Gly Gly Cys SerSer Lys 50 55 60 Trp Cys Arg Asp His Ala Arg Cys Cys Gly Arg 65 70 75211 20 PRT Conus striatus PEPTIDE (1)..(20) Xaa at residue 1 is Gln orpyro-Glu; Xaa at residue 12 is Trp or bromo-Trp 211 Xaa Asn Cys Cys AsnGly Gly Cys Ser Ser Lys Xaa Cys Arg Asp His 1 5 10 15 Ala Arg Cys Cys 20212 235 DNA Conus tessulatus 212 ggatccatga tgtctaaact gggagtcttgttgaccatgt gtctgcttct gtttcccctt 60 actgctgttc cgctggatgg agatcaacctgcagaccgac ctgcagagcg taggcaggac 120 attgcaactg acgatcatcc tttgtttgatcccgtcaaac ggtgctgcca caaatgctat 180 atgggatgca tcccttgttg catttagtaacgtgttgatg accaactttc tcgag 235 213 68 PRT Conus tessulatus 213 Gly SerMet Met Ser Lys Leu Gly Val Leu Leu Thr Met Cys Leu Leu 1 5 10 15 LeuPhe Pro Leu Thr Ala Val Pro Leu Asp Gly Asp Gln Pro Ala Asp 20 25 30 ArgPro Ala Glu Arg Arg Gln Asp Ile Ala Thr Asp Asp His Pro Leu 35 40 45 PheAsp Pro Val Lys Arg Cys Cys His Lys Cys Tyr Met Gly Cys Ile 50 55 60 ProCys Cys Ile 65 214 14 PRT Conus tessulatus PEPTIDE (1)..(14) Xaa atresidue 11 is Pro or Hyp; Xaa at residue 6 is Tyr, 125I-Tyr,mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 214 Cys CysHis Lys Cys Xaa Met Gly Cys Ile Xaa Cys Cys Ile 1 5 10 215 238 DNA Conustessulatus 215 ggatccatga tgtctaaact gggagtcttg ttgaccatct gtgtgcttctgtttcccctt 60 actgctgttc cgctggatgg agatcaacct gcagaccaac ctgcagagcgtacgcagaac 120 gagcagcatc ccttgtatga tcagaaaaga aagtgttgcc ggccgccatgcgccatgagc 180 tgcggcatgg ctaggtgttg ctattaatga taacgtgttg atgaccaactttctcgag 238 216 68 PRT Conus tessulatus 216 Gly Ser Met Met Ser Lys LeuGly Val Leu Leu Thr Ile Cys Val Leu 1 5 10 15 Leu Phe Pro Leu Thr AlaVal Pro Leu Asp Gly Asp Gln Pro Ala Asp 20 25 30 Gln Pro Ala Glu Arg ThrGln Asn Glu Gln His Pro Leu Tyr Asp Gln 35 40 45 Lys Arg Lys Cys Cys ArgPro Pro Cys Ala Met Ser Cys Gly Met Ala 50 55 60 Arg Cys Cys Tyr 65 21718 PRT Conus tessulatus PEPTIDE (1)..(18) Xaa at residue 5 and 6 is Proor Hyp; Xaa at residue 18 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr,O-sulpho-Tyr or O-phospho-Tyr 217 Lys Cys Cys Arg Xaa Xaa Cys Ala MetSer Cys Gly Met Ala Arg Cys 1 5 10 15 Cys Xaa 218 564 DNA Conus textile218 gagtcaaccc actgtcacgc caagagcgga cgccacagct aaggcaagaa ggatcgatag 60cagttcatga tgtctaaact gggagccttg ttgaccatct gtctacttct gttttccctt 120actgctgttc cgctggatgg agatcaacat gcagaccaac ctgcacagcg tctgcaggac 180cgcattccaa ctgaagatca tcccttattt gatcccaaca aacggtgttg cccgccggtg 240gcatgcaaca tgggatgcaa gccttgttgt ggatgaccag ctttgttatc gcggtctcat 300gaagtgtcta atgaataagt aaaacgattg cagtttcgtt cagatttgct gttgtatttt 360ggtctaaaga ttaatgacca aactgttctt ttgatccgga ttttcacgta tttctcgatt 420219 69 PRT Conus textile 219 Met Met Ser Lys Leu Gly Ala Leu Leu Thr IleCys Leu Leu Leu Phe 1 5 10 15 Ser Leu Thr Ala Val Pro Leu Asp Gly AspGln His Ala Asp Gln Pro 20 25 30 Ala Gln Arg Leu Gln Asp Arg Ile Pro ThrGlu Asp His Pro Leu Phe 35 40 45 Asp Pro Asn Lys Arg Cys Cys Pro Pro ValAla Cys Asn Met Gly Cys 50 55 60 Lys Pro Cys Cys Gly 65 220 16 PRT Conustextile PEPTIDE (1)..(16) Xaa at residue 3, 4 and 13 is Pro or Hyp 220Cys Cys Xaa Xaa Val Ala Cys Asn Met Gly Cys Lys Xaa Cys Cys Gly 1 5 1015 221 780 DNA Conus textile 221 ggatccagac gacaaagaag agtcaacccactgccacgtc aagagcagag cccacagcta 60 agacaagaag gatcgatagc agttcatgatgtttaaactg ggagtcttgt tgaccatctg 120 tctccttctg ttttccctta atgctgttccgttggatgga gatcaacctg cagaccaacc 180 tgcagagcgt ctgctggacg acatttcatttgaaaataat cccttttatg atcccgccaa 240 acggtgttgc aggacttgct tcggttgcacaccttgttgt ggatgaccag cctcatcaag 300 tgtctaacga ataagtaaag cgattgcagtctcgttcaga tttacttttg tattctggtc 360 taaagattaa tgaccaaact cttcttttgatccggatgta catatatttc tcgattccta 420 tccaacgcta gataagctaa tcacgacagatctgattttc tgtcaatgcc ttgctttttg 480 gtctctcata tcactcttgt ttatatttaatttctcgtca ctatatatat atatacacac 540 acacacacac ggaattccga ttgtccagtaccgttcttgg gatcgaggta ttgctgcgat 600 ggcttattct gtactctttt cttctgcgcttgatagtgat gtcttctact cccatctgtg 660 ctacccctgg cttgatcttt gataggcgtgtgcccttcac tggttataaa cccctctgat 720 cctactctct ggacgcctcg ggggcccaacctccaaataa agcgacatcc aatgaaaaaa 780 222 66 PRT Conus textile 222 MetMet Phe Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15Ser Leu Asn Ala Val Pro Leu Asp Gly Asp Gln Pro Ala Asp Gln Pro 20 25 30Ala Glu Arg Leu Leu Asp Asp Ile Ser Phe Glu Asn Asn Pro Phe Tyr 35 40 45Asp Pro Ala Lys Arg Cys Cys Arg Thr Cys Phe Gly Cys Thr Pro Cys 50 55 60Cys Gly 65 223 12 PRT Conus textile PEPTIDE (1)..(12) Xaa at residue 10is Pro or Hyp 223 Cys Cys Arg Thr Cys Phe Gly Cys Thr Xaa Cys Cys 1 5 10224 456 DNA Conus textile 224 ggaacagtca accccacagc cacgccaagagcagacagcc acagctacgt gaagaagggt 60 ggagagaggt tcatgatgtt gaaaatgggagtggtgctat tcatctttct ggtactgttt 120 cccctggcaa cgctccagct ggatgcagatcaacctgtag aacgatatgc ggagaacaaa 180 cagctcctca acccagatga aaggagggaaatcctattgc ctgctctgag gaagttctgc 240 tgtgattcga attggtgcca catttcggattgtgagtgct gctacggtta gcgccgaaca 300 tccatggcac tgtgctgggc ggtttcatcccaacaacgac agcgtttgtt gatttcatgt 360 atcattgcgc ccacgtctct tgtctaagaatgacgaacat gattgcactc tggttcagat 420 ttcgtgttct tttctgacaa taaatgacaaacctcc 456 225 70 PRT Conus textile 225 Met Met Leu Lys Met Gly Val ValLeu Phe Ile Phe Leu Val Leu Phe 1 5 10 15 Pro Leu Ala Thr Leu Gln LeuAsp Ala Asp Gln Pro Val Glu Arg Tyr 20 25 30 Ala Glu Asn Lys Gln Leu LeuAsn Pro Asp Glu Arg Arg Glu Ile Leu 35 40 45 Leu Pro Ala Leu Arg Lys PheCys Cys Asp Ser Asn Trp Cys His Asp 50 55 60 Cys Glu Cys Cys Tyr Gly 6570 226 17 PRT Conus textile PEPTIDE (1)..(17) Xaa at residue 14 is Gluor gamma-carboxy Glu; Xaa at residue 7 is Trp or bromo-Trp; Xaa atresidue 17 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho- Tyr 226 Phe Cys Cys Asp Ser Asn Xaa Cys His Ile Ser Asp CysXaa Cys Cys 1 5 10 15 Xaa 227 456 DNA Conus textile misc_feature(1)..(456) n may be any nucleotide 227 caaggaacag tcaaccccac agccacgccaagagcagaca gccacagcta cgtgaagaag 60 ggtggagaga ggttcgtgat gttgaaaatgggagtggtgc tattcatctt cctggtactg 120 tttcccctgg caacgctcca gctggatgcagatcaacctg tagaacgata tgcggagaac 180 aaacagctcc tcagcccaga tgaaaggagggaaatcatat tgcatgctct ggggacgcga 240 tgctgttctt gggatgtgtg cgaccacccgagttgtactt gctgcggtta gcgccgaaca 300 tccatggcgc tgtgctgggc ggttttatcccaacaacgac agcgtttgtt gatttcatgt 360 atcattgcgc ccacgtctct tgtctaagaatgacgaacat gattgcactc tggttcagat 420 ttcgtgttct tttctgacaa taaatgacaaaacncc 456 228 70 PRT Conus textile 228 Met Leu Lys Met Gly Val Val LeuPhe Ile Phe Leu Val Leu Phe Pro 1 5 10 15 Leu Ala Thr Leu Gln Leu AspAla Asp Gln Pro Val Glu Arg Tyr Ala 20 25 30 Glu Asn Lys Gln Leu Leu SerPro Asp Glu Arg Arg Glu Ile Ile Leu 35 40 45 His Ala Leu Gly Thr Arg CysCys Ser Trp Asp Val Cys Asp His Pro 50 55 60 Ser Cys Thr Cys Cys Gly 6570 229 15 PRT Conus textile PEPTIDE (1)..(15) Xaa at residue 10 is Proor Hyp; Xaa at residue 4 is Trp or bromo-Trp 229 Cys Cys Ser Xaa Asp ValCys Asp His Xaa Ser Cys Thr Cys Cys 1 5 10 15 230 235 DNA Conus textile230 ggatccatga tgtctaaact gggagtcttg ttgaccatct gtctgcttct gtttcccctt 60actgctcttc cgctggatgg agatcaaccc gcagaccaag ctgcagagcg tatgcaggcc 120gagcagcatc ccttgtttga tcagaaaaga cggtgctgca agtttccatg ccccgatagt 180tgcagatatt tgtgttgcgg gtgatgataa cgtgttgatg accaactttc tcgag 235 231 67PRT Conus textile 231 Gly Ser Met Met Ser Lys Leu Gly Val Leu Leu ThrIle Cys Leu Leu 1 5 10 15 Leu Phe Pro Leu Thr Ala Leu Pro Leu Asp GlyAsp Gln Pro Ala Asp 20 25 30 Gln Ala Ala Glu Arg Met Gln Ala Glu Gln HisPro Leu Phe Asp Gln 35 40 45 Lys Arg Arg Cys Cys Lys Phe Pro Cys Pro AspSer Cys Arg Tyr Leu 50 55 60 Cys Cys Gly 65 232 16 PRT Conus textilePEPTIDE (1)..(16) Xaa at residue 3 and 8 is Pro or Hyp; Xaa at residue13 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho-Tyr 232 Arg Cys Cys Lys Phe Xaa Cys Xaa Asp Ser Cys Arg XaaLeu Cys Cys 1 5 10 15 233 321 DNA Conus tulipa 233 cgacctcaag agggatcgatagcagttcat gtctaaactg ggagtcttgt tgacaatctg 60 tctgcttctg tttccccttactgctctgcc gatggatgga gatgaacctg cagaccgacc 120 tgcagagcgt atgcaggacaacatttcatc tgagcagcat cccttgtttg aggagagaca 180 cggatgttgc aaggggcccgaaggatgctc ctccagagaa tgcagacccc aacattgttg 240 cggtcgacga taacgtgttgagggccaact ttgttatcac ggctacgtca agtgtttagt 300 gaataagtaa aatgattgca g321 234 74 PRT Conus tulipa 234 Met Ser Lys Leu Gly Val Leu Leu Thr IleCys Leu Leu Leu Phe Pro 1 5 10 15 Leu Thr Ala Leu Pro Met Asp Gly AspGlu Pro Ala Asp Arg Pro Ala 20 25 30 Glu Arg Met Gln Asp Asn Ile Ser SerGlu Gln His Pro Leu Phe Glu 35 40 45 Glu Arg His Gly Cys Cys Lys Gly ProGlu Gly Cys Ser Ser Arg Glu 50 55 60 Cys Arg Pro Gln His Cys Cys Gly ArgArg 65 70 235 21 PRT Conus tulipa PEPTIDE (1)..(21) Xaa at residue 8 and14 is Glu or gamma-carboxy Glu; Xaa at residue 7 and 17 is Pro or Hyp235 His Gly Cys Cys Lys Gly Xaa Xaa Gly Cys Ser Ser Arg Xaa Cys Arg 1 510 15 Xaa Gln His Cys Cys 20 236 287 DNA Conus figulinus 236 caagaaggatcgatagcagt tcatgatgtc taaactggga gtcttgctga ccatctgtct 60 gcttctgattccccttactg ctctttcgct ggatggagat caacctgcag accgacctgc 120 agagcgtatgcaggatggaa tttcatctga acagcatccc atgtttgatc ccgtcagacg 180 gtgttgcccgtggccatgca acataggatg cgtaccttgt tgttgatgac cagttttgtt 240 atcgcggcctcatcaaatgt ctaatgaata agtaaaacga ttgcagt 287 237 67 PRT Conus figulinus237 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Ile 1 510 15 Pro Leu Thr Ala Leu Ser Leu Asp Gly Asp Gln Pro Ala Asp Arg Pro 2025 30 Ala Glu Arg Met Gln Asp Gly Ile Ser Ser Glu Gln His Pro Met Phe 3540 45 Asp Pro Val Arg Arg Cys Cys Pro Trp Pro Cys Asn Ile Gly Cys Val 5055 60 Pro Cys Cys 65 238 14 PRT Conus figulinus PEPTIDE (1)..(14) Xaa atresidue 3, 5 and 12 is Pro or Hyp; Xaa at residue 4 is Trp or bromo-Trp238 Cys Cys Xaa Xaa Xaa Cys Asn Ile Gly Cys Val Xaa Cys Cys 1 5 10 239283 DNA Conus figulinus 239 caagagggat cgatagcagt tcatgatgtt taaactgggagtcctgttga ccatctgtat 60 gcttctgttt ccctttactg ctcttccgct ggatggagagcaacctgcag accaacctgc 120 agagcgcatg cagtatgaca tgttacgtgc aatgaatccctggtttgatc ccgtcaaaag 180 gtgctgctcg aagaactgcg cagtatgcat cccttgttgcccgtaactga ccagcttgat 240 tatcgcggcc aaggctctaa tgaataagta aaacgattgcagt 283 240 67 PRT Conus figulinus 240 Met Met Phe Lys Leu Gly Val LeuLeu Thr Ile Cys Met Leu Leu Phe 1 5 10 15 Pro Phe Thr Ala Leu Pro LeuAsp Gly Glu Gln Pro Ala Asp Gln Pro 20 25 30 Ala Glu Arg Met Gln Tyr AspMet Leu Arg Ala Met Asn Pro Trp Phe 35 40 45 Asp Pro Val Lys Arg Cys CysSer Lys Asn Cys Ala Val Cys Ile Pro 50 55 60 Cys Cys Pro 65 241 14 PRTConus figulinus PEPTIDE (1)..(14) Xaa at residue 11 and 14 is Pro or Hyp241 Cys Cys Ser Lys Asn Cys Ala Val Cys Ile Xaa Cys Cys Xaa 1 5 10 242286 DNA Conus figulinus 242 caagagggat cgatagcagt tcatgatgtc taaactgagagtcttgttga ccttatgtct 60 gcttctgttt ccccttactg ctcttccgct gaatgaagatcaacctgcag agcgtatgca 120 ggacgacaat tcatctgagc agcacccctt gtatgaccacaaacgaaagt gttgccggtg 180 gccatgcccc gcaagatgcg gctcttgttg cctgtaataacgtgttggcc aactttgtta 240 tcacggccac gtcaaatgtt taatgaataa gtaaaacgattgcagt 286 243 64 PRT Conus figulinus 243 Met Met Ser Lys Leu Arg ValLeu Leu Thr Leu Cys Leu Leu Leu Phe 1 5 10 15 Pro Leu Thr Ala Leu ProLeu Asn Glu Asp Gln Pro Ala Glu Arg Met 20 25 30 Gln Asp Asp Asn Ser SerGlu Gln His Pro Leu Tyr Asp His Lys Arg 35 40 45 Lys Cys Cys Arg Trp ProCys Pro Ala Arg Cys Gly Ser Cys Cys Leu 50 55 60 244 15 PRT Conusfigulinus PEPTIDE (1)..(15) Xaa at residue 5 and 7 is Pro or Hyp; Xaa atresidue 4 is Trp or bromo-Trp 244 Cys Cys Arg Xaa Xaa Cys Xaa Ala ArgCys Gly Ser Cys Cys Leu 1 5 10 15 245 301 DNA Conus figulinus 245caagagggat cgatagcagt tcatgatgtc taaactggga gtcttgttga ccttatgtct 60gcttctgttt cccctgactg ctcttccgct ggatgaagat caagctgcag accgacctgc 120agagcgtatg cagggcatgt catctgaaca gcatcccttc tttgatcccg tcaaacggtg 180ttgcgagttg tcacgctgcc ttggatgcgt cccttgttgc acatcttaat aacgtgtgga 240tgaccaactg tgttatcacg gccacgtcaa gtgtctaatg aataagtaaa atgattgcag 300 t301 246 68 PRT Conus figulinus 246 Met Met Ser Lys Leu Gly Val Leu LeuThr Leu Cys Leu Leu Leu Phe 1 5 10 15 Pro Leu Thr Ala Leu Pro Leu AspGlu Asp Gln Ala Ala Asp Arg Pro 20 25 30 Ala Glu Arg Met Gln Gly Met SerSer Glu Gln His Pro Phe Phe Asp 35 40 45 Pro Val Lys Arg Cys Cys Glu LeuSer Arg Cys Leu Gly Cys Val Pro 50 55 60 Cys Cys Thr Ser 65 247 16 PRTConus figulinus PEPTIDE (1)..(16) Xaa at residue 3 and 12 is Pro or Hyp247 Cys Cys Xaa Leu Ser Arg Cys Leu Gly Cys Val Xaa Cys Cys Thr Ser 1 510 15 248 301 DNA Conus figulinus 248 caagagggat cgatagcagt tcatgatgtctaaactggga gtcttgttga ccttatgtct 60 gcttctgttt cccctgactg ctcttccgctggatgaagat caacctgcag accgacctgc 120 agagcgtatg cagggcatgt catctgaacagcatcccttc tttgatcccg tcaaacggtg 180 ttgcgagttg tcaaaatgcc atggatgcgtcccttgttgc ataccttaat aacgtgcgga 240 tgaccaactg tgttatcacg gccacgtcaagtgtctaatg aataagtaaa atgattgcag 300 t 301 249 68 PRT Conus figulinus249 Met Met Ser Lys Leu Gly Val Leu Leu Thr Leu Cys Leu Leu Leu Phe 1 510 15 Pro Leu Thr Ala Leu Pro Leu Asp Glu Asp Gln Pro Ala Asp Arg Pro 2025 30 Ala Glu Arg Met Gln Gly Met Ser Ser Glu Gln His Pro Phe Phe Asp 3540 45 Pro Val Lys Arg Cys Cys Glu Leu Ser Lys Cys His Gly Cys Val Pro 5055 60 Cys Cys Ile Pro 65 250 16 PRT Conus figulinus PEPTIDE (1)..(16)Xaa at residue 3 is Glu or gamma-carboxy Glu; Xaa at residue 12 and 16is Pro or Hyp 250 Cys Cys Xaa Leu Ser Lys Cys His Gly Cys Val Xaa CysCys Ile Xaa 1 5 10 15 251 298 DNA Conus quercinus 251 caagagggatcgatagcagt tcatgatgtc taaactcgga gtcttgttga ccatctgtct 60 ggttctgtttccccttacag ctcttcagct ggatggagat caacctgcag accgacctgc 120 agagcgtacgcaggacattt catctgaaca gtatcgaaag tttgatcaga gacagaggtg 180 ttgccggtggccatgccccg gtagttgcag atgctgccgt tatcgttaac gtgttggtga 240 ccagctttgttatcacgacc acgccaagtg tctaacgaat aagtaaaatg attgcagt 298 252 68 PRTConus quercinus 252 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys LeuVal Leu Phe 1 5 10 15 Pro Leu Thr Ala Leu Gln Leu Asp Gly Asp Gln ProAla Asp Arg Pro 20 25 30 Ala Glu Arg Thr Gln Asp Ile Ser Ser Glu Gln TyrArg Lys Phe Asp 35 40 45 Gln Arg Gln Arg Cys Cys Arg Trp Pro Cys Pro GlySer Cys Arg Cys 50 55 60 Cys Arg Tyr Arg 65 253 18 PRT Conus quercinusPEPTIDE (1)..(18) Xaa at residue 1 is Gln or pyro-Glu; Xaa at residue 7and 9 is Pro or Hyp; Xaa at residue 6 is Trp or bromo-Trp; Xaa atresidue 17 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho-Tyr 253 Xaa Arg Cys Cys Arg Xaa Xaa Cys Xaa Gly Ser Cys ArgCys Cys Arg 1 5 10 15 Xaa Arg 254 313 DNA Conus quercinus 254 caagagggatcgatagcagt tcatgatgtc taaactggga gtcttgttga ccatctgtct 60 gcttctgtttccccttactg ctcttccact ggatggagat caacctgcag atcaatctgc 120 agagcgacctgcagagcgta cgcaggacga cattcagcag catccgttat atgatccgaa 180 aagaaggtgttgccgttatc catgccccga cagctgccac ggatcttgct gctataagtg 240 ataacatgttgatggccagc tttgttatca cggccacgtc aagtgtctaa tgaataagta 300 aaacgattgcagt 313 255 72 PRT Conus quercinus 255 Met Met Ser Lys Leu Gly Val LeuLeu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Pro Leu Thr Ala Leu Pro LeuAsp Gly Asp Gln Pro Ala Asp Gln Ser 20 25 30 Ala Glu Arg Pro Ala Glu ArgThr Gln Asp Asp Ile Gln Gln His Pro 35 40 45 Leu Tyr Asp Pro Lys Arg ArgCys Cys Arg Tyr Pro Cys Pro Asp Ser 50 55 60 Cys His Gly Ser Cys Cys TyrLys 65 70 256 18 PRT Conus quercinus PEPTIDE (1)..(18) Xaa at residue 6and 8 is Pro or Hyp; Xaa at residue 5 and 17 is Tyr, 125I-Tyr,mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 256 Arg CysCys Arg Xaa Xaa Cys Xaa Asp Ser Cys His Gly Ser Cys Cys 1 5 10 15 XaaLys 257 256 DNA Conus wittigi 257 ggatccatga tgtctaaact gggagtcttgttgaccatct gtctgcttct gtttcccatt 60 actgctcttc cggtgggtgg agatcagcctgcagaccgac ttgcagagcg tatgcaggac 120 gacacttcat ctgagcagca tccctttgaaaagagactac catcatgttg cgactttgag 180 aggctttgcg tagtaccagc atgcatacgtcatcagtgtt gcacaggata acgtgttgat 240 gaccaacttt ctcgag 256 258 74 PRTConus wittigi 258 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys LeuLeu Leu Phe 1 5 10 15 Pro Ile Thr Ala Leu Pro Val Gly Gly Asp Gln ProAla Asp Arg Leu 20 25 30 Ala Glu Arg Met Gln Asp Asp Thr Ser Ser Glu GlnHis Pro Phe Glu 35 40 45 Lys Arg Leu Pro Ser Cys Cys Asp Phe Glu Arg LeuCys Val Val Pro 50 55 60 Ala Cys Ile Arg His Gln Cys Cys Thr Gly 65 70259 23 PRT Conus wittigi PEPTIDE (1)..(23) Xaa at residue 8 is Glu orgamma-carboxy Glu; Xaa at residue 2 and 14 is Pro or Hyp 259 Leu Xaa SerCys Cys Asp Phe Xaa Arg Leu Cys Val Val Xaa Ala Cys 1 5 10 15 Ile ArgHis Gln Cys Cys Thr 20 260 14 PRT Conus betulinus PEPTIDE (1)..(14) Xaaat residue 11 is Pro or Hyp; Xaa at residue 14 is Trp or bromo-Trp 260Cys Cys Lys Gln Ser Cys Thr Thr Cys Met Xaa Cys Cys Xaa 1 5 10 261 259DNA Conus tulipa misc_feature (1)..(259) n may be any nucleotide 261ggatccatga tgtctaaact gggagtcttg ttgacaatct gtctgcttct gtttcccctt 60actgctctgc cgatggatgg agatgaacct gcagaccgac ctgcagagcg tatgcaggac 120aacatttcat ctgagcagca tcccttgttt gaggagagac acggatgttg cgaggggccg 180aagggatgct cctccagaga atgcagaccc caacattgtt gcggtcgacg ataacgtgtt 240gatgaccaac tntctcgag 259 262 75 PRT Conus tulipa 262 Met Met Ser Lys LeuGly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Pro Leu Thr AlaLeu Pro Met Asp Gly Asp Glu Pro Ala Asp Arg Pro 20 25 30 Ala Glu Arg MetGln Asp Asn Ile Ser Ser Glu Gln His Pro Leu Phe 35 40 45 Glu Glu Arg HisGly Cys Cys Glu Gly Pro Lys Gly Cys Ser Ser Arg 50 55 60 Glu Cys Arg ProGln His Cys Cys Gly Arg Arg 65 70 75 263 21 PRT Conus tulipa PEPTIDE(1)..(21) Xaa at residue 5 and 14 is Glu or gamma-carboxy Glu; Xaa atresidue 7 and 17 is Pro or Hyp 263 His Gly Cys Cys Xaa Gly Xaa Lys GlyCys Ser Ser Arg Xaa Cys Arg 1 5 10 15 Xaa Gln His Cys Cys 20 264 262 DNAConus aurisiacus misc_feature (1)..(262) n may be any nucleotide 264ggatccatga tgtctaaact gggagtcttg ttgaccatct gtctacttct gtttcccctt 60actgcttttc cgatggatgg agatcaacct gcagaccaac ctgcagatcg tatgcaggac 120gacatttcat ctgagcagta tcccttgttt gataagagac aaaagtgttg cactgggagg 180aaggggtcat gctccggcaa agcatgcaaa aatctcaaat gttgctctgg acgataacgt 240gttgatgacc aactttctcg an 262 265 76 PRT Conus aurisiacus 265 Met Met SerLys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Pro LeuThr Ala Phe Pro Met Asp Gly Asp Gln Pro Ala Asp Gln Pro 20 25 30 Ala AspArg Met Gln Asp Asp Ile Ser Ser Glu Gln Tyr Pro Leu Phe 35 40 45 Asp LysArg Gln Lys Cys Cys Thr Gly Arg Lys Gly Ser Cys Ser Gly 50 55 60 Lys AlaCys Lys Asn Leu Lys Cys Cys Ser Gly Arg 65 70 75 266 23 PRT Conusaurisiacus PEPTIDE (1)..(23) Xaa at residue 1 is Gln or pyro-Glu 266 XaaLys Cys Cys Thr Gly Arg Lys Gly Ser Cys Ser Gly Lys Ala Cys 1 5 10 15Lys Asn Leu Lys Cys Cys Ser 20 267 239 DNA Conus betulinus 267ggatccatga tgtctaaact gggagtcttg ttgaccatct gtctgcttct gtttcccctt 60actgctgttc cgttggatgg agatcaacct gcagaccaac ctgcagagcg tatgcagaac 120gagcagcatc cctcgtttga tcagaaaaga aggtgctgcc ggtggccatg ccccagtata 180tgcggcatgg ctaggtgttg cttcgtcatg ataacgtgtt gatgaccaac tttctcgag 239 26871 PRT Conus betulinus 268 Met Met Ser Lys Leu Gly Val Leu Leu Thr IleCys Leu Leu Leu Phe 1 5 10 15 Pro Leu Thr Ala Val Pro Leu Asp Gly AspGln Pro Ala Asp Gln Pro 20 25 30 Ala Glu Arg Met Gln Asn Glu Gln His ProSer Phe Asp Gln Lys Arg 35 40 45 Arg Cys Cys Arg Trp Pro Cys Pro Ser IleCys Gly Met Ala Arg Cys 50 55 60 Cys Phe Val Met Ile Thr Cys 65 70 26923 PRT Conus betulinus PEPTIDE (1)..(23) Xaa at residue 6 and 8 is Proor Hyp; Xaa at residue 5 is Trp or bromo-Trp 269 Arg Cys Cys Arg Xaa XaaCys Xaa Ser Ile Cys Gly Met Ala Arg Cys 1 5 10 15 Cys Phe Val Met IleThr Cys 20 270 226 DNA Conus betulinus misc_feature (1)..(226) n may beany nucleotide 270 ggatccatga tgtctaaact gggagtcttg ttgatcatctgtctgcttct gtttcccctt 60 actgctgttc cgctggatgg agatcagcct gcagagcgtacgcagatcga gcagcatccc 120 ttgtttgacc agaaaagaag gtgttgccgg tggccatgccccagtagatg cggcatggct 180 aggtgttgct tcgtcatgat aacgtgttga tgancgacctctcnag 226 271 67 PRT Conus betulinus 271 Met Met Ser Lys Leu Gly ValLeu Leu Ile Ile Cys Leu Leu Leu Phe 1 5 10 15 Pro Leu Thr Ala Val ProLeu Asp Gly Asp Gln Pro Ala Glu Arg Thr 20 25 30 Gln Ile Glu Gln His ProLeu Phe Asp Gln Lys Arg Arg Cys Cys Arg 35 40 45 Trp Pro Cys Pro Ser ArgCys Gly Met Ala Arg Cys Cys Phe Val Met 50 55 60 Ile Thr Cys 65 272 23PRT Conus betulinus PEPTIDE (1)..(23) Xaa at residue 6 and 8 is Pro orHyp; Xaa at residue 5 is Trp or bromo-Trp 272 Arg Cys Cys Arg Xaa XaaCys Xaa Ser Arg Cys Gly Met Ala Arg Cys 1 5 10 15 Cys Phe Val Met IleThr Cys 20 273 262 DNA Conus parius 273 ggatccatga tgtctaaact gggagtcttgttgaccatct gtctgcttct gtttcccctt 60 actgctcttc cgatggatgg tgatcaacctgcagaccgac ttgtagagcg tatgcaggac 120 aacatttcat ctgagcagca tcccttctttgaaaagagaa gaggaggctg ttgcacacct 180 ccgaagaaat gcaaagaccg agcctgcaaacctgcacgtt gctgcggccc aggataacgt 240 gttgatgacc aactttctcg cc 262 274 76PRT Conus parius 274 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys LeuLeu Leu Phe 1 5 10 15 Pro Leu Thr Ala Leu Pro Met Asp Gly Asp Gln ProAla Asp Arg Leu 20 25 30 Val Glu Arg Met Gln Asp Asn Ile Ser Ser Glu GlnHis Pro Phe Phe 35 40 45 Glu Lys Arg Arg Gly Gly Cys Cys Thr Pro Pro LysLys Cys Lys Asp 50 55 60 Arg Ala Cys Lys Pro Ala Arg Cys Cys Gly Pro Gly65 70 75 275 24 PRT Conus parius PEPTIDE (1)..(24) Xaa at residue 7, 8,18 and 24 is Pro or Hyp 275 Arg Gly Gly Cys Cys Thr Xaa Xaa Lys Lys CysLys Asp Arg Ala Cys 1 5 10 15 Lys Xaa Ala Arg Cys Cys Gly Xaa 20 276 259DNA Conus parius 276 ggatccatga tgtctaaact gggagtcttg ttgaccatctgtctgcttct gtttcccctt 60 actgctcttc cgatggatgg tgatcaacct gcagaccgacttgtagagcg tatgcaggac 120 aacatttcat ctgagcagca tcccttcttt gaaaagagaagaggctgttg cacacctccg 180 aggaaatgca aagaccgagc ctgcaaacct gcacgttgttgcggcccagg ataacgtgtt 240 gatgaccaac tttctcgag 259 277 75 PRT Conusparius 277 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu LeuPhe 1 5 10 15 Pro Leu Thr Ala Leu Pro Met Asp Gly Asp Gln Pro Ala AspArg Leu 20 25 30 Val Glu Arg Met Gln Asp Asn Ile Ser Ser Glu Gln His ProPhe Phe 35 40 45 Glu Lys Arg Arg Gly Cys Cys Thr Pro Pro Arg Lys Cys LysAsp Arg 50 55 60 Ala Cys Lys Pro Ala Arg Cys Cys Gly Pro Gly 65 70 75278 23 PRT Conus parius PEPTIDE (1)..(23) Xaa at residue 6, 7, 17 and 23is Pro or Hyp 278 Arg Gly Cys Cys Thr Xaa Xaa Arg Lys Cys Lys Asp ArgAla Cys Lys 1 5 10 15 Xaa Ala Arg Cys Cys Gly Xaa 20 279 241 DNA Conuscoronatus 279 ggatccatga tgtctaaact gggagtcttg ttgaccatct gtctgcttctgtttccaatt 60 actgcccttc cgctggatga agatcaacct gcagaccgac ctgcagagcgtatgcaggac 120 attgcaactg aacagcatcc cttgtttgat cccgtcaaac ggtgctgcgattggccatgc 180 atcccaggat gcaccccttg ttgcttgcct tgataacgtg ttgatgaccaactttctcga 240 g 241 280 68 PRT Conus coronatus 280 Met Met Ser Lys LeuGly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Pro Ile Thr AlaLeu Pro Leu Asp Glu Asp Gln Pro Ala Asp Arg Pro 20 25 30 Ala Glu Arg MetGln Asp Ile Ala Thr Glu Gln His Pro Leu Phe Asp 35 40 45 Pro Val Lys ArgCys Cys Asp Trp Pro Cys Ile Pro Gly Cys Thr Pro 50 55 60 Cys Cys Leu Pro65 281 16 PRT Conus coronatus PEPTIDE (1)..(16) Xaa at residue 5, 8, 12and 16 is Pro or Hyp; Xaa at residue 4 is Trp or bromo-Trp 281 Cys CysAsp Xaa Xaa Cys Ile Xaa Gly Cys Thr Xaa Cys Cys Leu Xaa 1 5 10 15 282244 DNA Conus musicus 282 ggatccatga tgtctaaact gggagtcctg ttgaccatctgtctgcttct gtttcctctt 60 tctgctcttc cgatggatga agatcaactt gcagacctacctgcagagcg tatgcgggac 120 actgcaactg tagatcatcc ctcctatgat cctgacaaagcgtgctgcga gcagagctgt 180 acaacatgct ttccgtgctg ctagccttga acacagtaacgtgttgatga ccaactttct 240 cgag 244 283 65 PRT Conus musicus 283 Met MetSer Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 ProLeu Ser Ala Leu Pro Met Asp Glu Asp Gln Leu Ala Asp Leu Pro 20 25 30 AlaGlu Arg Met Arg Asp Thr Ala Thr Val Asp His Pro Ser Tyr Asp 35 40 45 ProAsp Lys Ala Cys Cys Glu Gln Ser Cys Thr Thr Cys Phe Pro Cys 50 55 60 Cys65 284 14 PRT Conus musicus PEPTIDE (1)..(14) Xaa at residue4 is Glu orgamma-carboxy Glu; Xaa at residue 12 is Pro or Hyp 284 Ala Cys Cys XaaGln Ser Cys Thr Thr Cys Phe Xaa Cys Cys 1 5 10 285 14 PRT Conusbetulinus PEPTIDE (1)..(14) Xaa at residue 4 is Glu or gamma-carboxyGlu; Xaa at residue 12 is Pro or Hyp 285 Ala Cys Cys Xaa Gln Ser Cys ThrThr Cys Met Xaa Cys Cys 1 5 10 286 14 PRT Conus betulinus PEPTIDE(1)..(14) Xaa at residue 3 is Glu or gamma-carboxy Glu; Xaa at residue11 is Pro or Hyp; Xaa at residue 14 is Trp or bromo-Trp 286 Cys Cys XaaGln Ser Cys Thr Thr Cys Met Xaa Cys Cys Xaa 1 5 10 287 235 DNA Conuspennaceus 287 ggatccatga tgtctaaact gggagtcttg ttgaccatct gtctgcttctgtttcccctt 60 actgctcttc cgctggatgg agatcaacct gcataccaag ctgcagagcgtatgcaggcc 120 gagcatcatc ccttgtttga tcagaaaaga cggtgctgca agtttccatgccccgatagt 180 tgcaaatatt tgtgttgcgg gtgatgataa catgttgatg accaactttcttgag 235 288 65 PRT Conus pennaceus 288 Met Met Ser Lys Leu Gly Val LeuLeu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Pro Leu Thr Ala Leu Pro LeuAsp Gly Asp Gln Pro Ala Tyr Gln Ala 20 25 30 Ala Glu Arg Met Gln Ala GluHis His Pro Leu Phe Asp Gln Lys Arg 35 40 45 Arg Cys Cys Lys Phe Pro CysPro Asp Ser Cys Lys Tyr Leu Cys Cys 50 55 60 Gly 65 289 16 PRT Conuspennaceus PEPTIDE (1)..(16) Xaa at residue 6 and 8 is Pro or Hyp; Xaa atresidue 13 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho-Tyr 289 Arg Cys Cys Lys Phe Xaa Cys Xaa Asp Ser Cys Lys XaaLeu Cys Cys 1 5 10 15 290 241 DNA Conus pulicarius 290 ggatccatgatgtctaaact gggagtcttg ttgaccatct gtctgcttct gtttcccctt 60 actgctcttccgatggatgg tgatcaactt gcagaccgac ttgtagagcg tatgcaggac 120 aacatttcatctgagcagca tcccttcttt gatcccgtca aacggtgttg cgtcagctgt 180 tacatgggatgcatcccttg ttgcttctag taataacgtg ttgatgacca actttctcga 240 g 241 291 67PRT Conus pulicarius 291 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile CysLeu Leu Leu Phe 1 5 10 15 Pro Leu Thr Ala Leu Pro Met Asp Gly Asp GlnLeu Ala Asp Arg Leu 20 25 30 Val Glu Arg Met Gln Asp Asn Ile Ser Ser GluGln His Pro Phe Phe 35 40 45 Asp Pro Val Lys Arg Cys Cys Val Ser Cys TyrMet Gly Cys Ile Pro 50 55 60 Cys Cys Phe 65 292 14 PRT Conus pulicariusPEPTIDE (1)..(14) Xaa at residue 11 is Pro or Hyp; Xaa at residue 6 isTyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr292 Cys Cys Val Ser Cys Xaa Met Gly Cys Ile Xaa Cys Cys Phe 1 5 10 293244 DNA Conus pulicarius 293 ggatccatga tgtctaaact gggagtcttg ttgaccgtctgtctgcttct gtgtcccctt 60 actgctcttc cactggatga agatcaactt gcagaccgacctgcagagcg tatgcaggat 120 gacacttcag ctgcacagat tttcgggttt gatcccgtcaaacggtgctg caaattgcta 180 tgctactcgg gatgcactcc ttgttgccat atttgataacgtgttgatga ccaactttct 240 cgag 244 294 67 PRT Conus pulicarius 294 MetMet Ser Lys Leu Gly Val Leu Leu Thr Val Cys Leu Leu Leu Cys 1 5 10 15Pro Leu Thr Ala Leu Pro Leu Asp Glu Asp Gln Leu Ala Asp Arg Pro 20 25 30Ala Glu Arg Met Gln Asp Asp Thr Ser Ala Ala Gln Ile Phe Gly Phe 35 40 45Asp Pro Val Lys Arg Cys Cys Lys Leu Leu Cys Gly Cys Thr Pro Cys 50 55 60Cys His Ile 65 295 16 PRT Conus pulicarius PEPTIDE (1)..(16) Xaa atresidue 12 is Pro or Hyp; Xaa at residue 7 is Tyr, 125I-Tyr,mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 295 Cys CysLys Leu Leu Cys Xaa Ser Gly Cys Thr Xaa Cys Cys His Ile 1 5 10 15 296259 DNA Conus rattus 296 ggatccatga tgtctaaact gggagtcttg ttgaccatctgtctgcttgt gtttccgctt 60 actgctcttc cgatggatgg tgatcaacct gcagaccgacttgtagagcg tatacaggac 120 aacatttcat ctgagcagca tcccttcttt gaaaagagaagaggctgttg cgcacctccg 180 aggaaatgca aagaccgagc ctgcaaacct gcacgttgctgcggcccagg ataacgtgtt 240 gatgaccaac tttctcgag 259 297 75 PRT Conusrattus 297 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu ValPhe 1 5 10 15 Pro Leu Thr Ala Leu Pro Met Asp Gly Asp Gln Pro Ala AspArg Leu 20 25 30 Val Glu Arg Ile Gln Asp Asn Ile Ser Ser Glu Gln His ProPhe Phe 35 40 45 Glu Lys Arg Arg Gly Cys Cys Ala Pro Pro Arg Lys Cys LysAsp Arg 50 55 60 Ala Cys Lys Pro Ala Arg Cys Cys Gly Pro Gly 65 70 75298 23 PRT Conus rattus PEPTIDE (1)..(23) Xaa at residue 6, 7, 17 and 23is Pro or Hyp 298 Arg Gly Cys Cys Ala Xaa Xaa Arg Lys Cys Lys Asp ArgAla Cys Lys 1 5 10 15 Xaa Ala Arg Cys Cys Gly Xaa 20 299 262 DNA Conusstercusmuscarum 299 ggatccatga tgtctaaact gggagtcttg ttgacaatctgtctgcttct gtttcccctt 60 attgctcttc cgctggatgg agatcaacct gcagaccgacctgcagagcg tatgcaggac 120 gacatttcat ctgagaagca tcccttgttt gataagagacaacggtgttg caatgggcgg 180 aggggatgct ccagcagatg gtgcagagat cactcacgttgttgcggtcg acgataacgt 240 gttgatgacc aactttctcg ag 262 300 76 PRT Conusstercusmuscarum 300 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys LeuLeu Leu Phe 1 5 10 15 Pro Leu Ile Ala Leu Pro Leu Asp Gly Asp Gln ProAla Asp Arg Pro 20 25 30 Ala Glu Arg Met Gln Asp Asp Ile Ser Ser Glu LysHis Pro Leu Phe 35 40 45 Asp Lys Arg Gln Arg Cys Cys Asn Gly Arg Arg GlyCys Ser Ser Arg 50 55 60 Trp Cys Arg Asp His Ser Arg Cys Cys Gly Arg Arg65 70 75 301 22 PRT Conus stercusmuscarum PEPTIDE (1)..(22) Xaa atresidue 1 is Gln or pyro-Glu; Xaa at residue 14 is Trp or bromo-Trp 301Xaa Arg Cys Cys Asn Gly Arg Arg Gly Cys Ser Ser Arg Xaa Cys Arg 1 5 1015 Asp His Ser Arg Cys Cys 20 302 241 DNA Conus ebraceus 302 ggatccatgatgtctaaact gggagtcttg ttgaccatct gtctgcttct gtttcccctt 60 actgctcttccactggatga aggtcaacct gcagacctac ctgcagagcg tatgcaggac 120 attgcaactgaacagcatcc cttgtttgat cctgtcaaac ggtgttgcga gcagccatgc 180 tacatgggatgcatcccttg ttgcttctaa taataacgtg ttgatgacca actttctcga 240 g 241 303 67PRT Conus ebraceus 303 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile CysLeu Leu Leu Phe 1 5 10 15 Pro Leu Thr Ala Leu Pro Leu Asp Glu Gly GlnPro Ala Asp Leu Pro 20 25 30 Ala Glu Arg Met Gln Asp Ile Ala Thr Glu GlnHis Pro Leu Phe Asp 35 40 45 Pro Val Lys Arg Cys Cys Glu Gln Pro Cys TyrMet Gly Cys Ile Pro 50 55 60 Cys Cys Phe 65 304 15 PRT Conus ebraceusPEPTIDE (1)..(15) Xaa at residue 3 is Glu or gamma-carboxy Glu; Xaa atresidue 5 and 12 is Pro or Hyp; Xaa at residue 7 is Tyr, 125I-Tyr,mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho- Tyr 304 Cys CysXaa Gln Xaa Cys Xaa Met Gly Cys Ile Xaa Cys Cys Phe 1 5 10 15 305 241DNA Conus ebraceus 305 ggatccatga tgtctaaact gggagtcttg ttgaccatctgtctgcttct gtttcccctt 60 actgctcttc cactggatga agatcaacct gcagacctacctgcagagcg tatgcaggac 120 attgcaactg aacagcatcc cttgtttgat cctgtcaaacggtgctgcgc gcagccatgc 180 tacatgggat gcatcccttg ttgcttctaa taataacgtgttgatgacca actttctcga 240 g 241 306 67 PRT Conus ebraceus 306 Met MetSer Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 ProLeu Thr Ala Leu Pro Leu Asp Glu Asp Gln Pro Ala Asp Leu Pro 20 25 30 AlaGlu Arg Met Gln Asp Ile Ala Thr Glu Gln His Pro Leu Phe Asp 35 40 45 ProVal Lys Arg Cys Cys Ala Gln Pro Cys Tyr Met Gly Cys Ile Pro 50 55 60 CysCys Phe 65 307 15 PRT Conus ebraceus PEPTIDE (1)..(15) Xaa at residue 5and 12 is Pro or Hyp; Xaa at residue 7 is Tyr, 125I-Tyr, mono-iodo-Tyr,di-iodo-Tyr, O-sulpho- Tyr or O-phospho-Tyr 307 Cys Cys Ala Gln Xaa CysXaa Met Gly Cys Ile Xaa Cys Cys Phe 1 5 10 15 308 238 DNA Conus flavidus308 ggatccatga tgtctaaact gggagtcttg ttgaccatct gtctgcttct gtttcccctt 60actgctgttc cgttggatgg agatcaacct gcagaccagc ctgcagagcg tatgcagaac 120gagcagcatc ccttgtttga tcagaaaaga aggtgctgcc ggtggccatg ccccagtata 180tgcggcatgg ctaggtgttg ctcgtcatga taacgtgttg atgaccaact ttctcgag 238 30967 PRT Conus flavidus 309 Met Met Ser Lys Leu Gly Val Leu Leu Thr IleCys Leu Leu Leu Phe 1 5 10 15 Pro Leu Thr Ala Val Pro Leu Asp Gly AspGln Pro Ala Asp Gln Pro 20 25 30 Ala Glu Arg Met Gln Asn Glu Gln His ProLeu Phe Asp Gln Lys Arg 35 40 45 Arg Cys Cys Arg Trp Pro Cys Pro Ser IleCys Gly Met Ala Arg Cys 50 55 60 Cys Ser Ser 65 310 19 PRT Conusflavidus PEPTIDE (1)..(19) Xaa at residue 6 and 8 is Pro or Hyp; Xaa atresidue 5 is Trp or bromo-Trp 310 Arg Cys Cys Arg Xaa Xaa Cys Xaa SerIle Cys Gly Met Ala Arg Cys 1 5 10 15 Cys Ser Ser 311 245 DNA Conusmiliaris misc_feature (1)..(245) n may be any nucleotide 311 ggatccatgatgtctaaact gggagtcttg ttgaccatct gtctgcttct gtttccaatt 60 actgcccttccactggatga agatcaacct gcagaccgac ctgcagagcg tatgcaggac 120 attgcaactgaacagcatcc cttgtttgat cccgtcaaac ggtgttgcga ttggccatgc 180 agcgcaggatgctacccttg ttgcttccct taataacgtg ttgatgacca actnangnaa 240 aaaaa 245 31268 PRT Conus miliaris 312 Met Met Ser Lys Leu Gly Val Leu Leu Thr IleCys Leu Leu Leu Phe 1 5 10 15 Pro Ile Thr Ala Leu Pro Leu Asp Glu AspGln Pro Ala Asp Arg Pro 20 25 30 Ala Glu Arg Met Gln Asp Ile Ala Thr GluGln His Pro Leu Phe Asp 35 40 45 Pro Val Lys Arg Cys Cys Asp Trp Pro CysSer Ala Gly Cys Tyr Pro 50 55 60 Cys Cys Phe Pro 65 313 16 PRT Conusmiliaris PEPTIDE (1)..(16) Xaa at residue 5, 12 and 16 is Pro or Hyp;Xaa at residue 4 is Trp or bromo-Trp; Xaa at residue 11 is Tyr,125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho -Tyr 313Cys Cys Asp Xaa Xaa Cys Ser Ala Gly Cys Xaa Xaa Cys Cys Phe Xaa 1 5 1015 314 230 DNA Conus miliaris misc_feature (1)..(230) n may be anynucleotide 314 ggatccatga tgtctaaact gggagtggtg ccattcgtct ttctggtcctgtttcccctg 60 gcaacactcc aactggatgc agatcaacct gcagaccgac ctgcgcgtaaaaagggcatt 120 gcaactaaac ggcatccctt gtctgatcct gtcagagggt gttgccctccaatgtgcaca 180 ccatgcttcc cttgctgttt tcgttaataa cgtgttgatg natgatgnan230 315 66 PRT Conus miliaris 315 Met Met Ser Lys Leu Gly Val Val ProPhe Val Phe Leu Val Leu Phe 1 5 10 15 Pro Leu Ala Thr Leu Gln Leu AspAla Asp Gln Pro Ala Asp Arg Pro 20 25 30 Ala Arg Lys Lys Gly Ile Ala ThrLys Arg His Pro Leu Ser Asp Pro 35 40 45 Val Arg Gly Cys Cys Pro Pro MetCys Thr Pro Cys Phe Pro Cys Cys 50 55 60 Phe Arg 65 316 16 PRT Conusmiliaris PEPTIDE (1)..(16) Xaa at residue 4, 9 and 12 is Pro or Hyp; Xaaat residue 5 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyror O-phospho-Tyr 316 Gly Cys Cys Xaa Xaa Met Cys Thr Xaa Cys Phe Xaa CysCys Phe Arg 1 5 10 15 317 295 DNA Conus ammiralis 317 caagagggatcgatagcagt tcatgatgtc taaactggga gtcttgttga ccatctgtct 60 gcttctgtttccccttactg ctcttccgct ggatggagat caacctgcag accaagctgc 120 agagcgtatgcaggccgagc agcatccctt gtttgatcag aaaagacggt gttgcaggtt 180 tccatgccccgatacttgca gacatttgtg ttgcgggtga tgataacgtg ctgatgaccc 240 actttgtcatcacggctacg tcaagtgtct aatgaataag taaaatgatt gcagt 295 318 65 PRT Conusammiralis 318 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu LeuLeu Phe 1 5 10 15 Pro Leu Thr Ala Leu Pro Leu Asp Gly Asp Gln Pro AlaAsp Gln Ala 20 25 30 Ala Glu Arg Met Gln Ala Glu Gln His Pro Leu Phe AspGln Lys Arg 35 40 45 Arg Cys Cys Arg Phe Pro Cys Pro Asp Thr Cys Arg HisLeu Cys Cys 50 55 60 Gly 65 319 16 PRT Conus ammiralis PEPTIDE (1)..(16)Xaa at residue 6 and 8 is Pro or Hyp 319 Arg Cys Cys Arg Phe Xaa Cys XaaAsp Thr Cys Arg His Leu Cys Cys 1 5 10 15 320 267 DNA Conus ammiralis320 caagagggat cgatagcagt tcatgatgtt taaactggga gtcttgctga ccatctgtct 60acttctgttt tcccttaatg ctgttccgct ggatggagat caacctgcag accaacctgc 120agagcgtctg ctggacgaca tttcatctga aaataatccc ttttatgatc ccgccaaacg 180gtgttgcatg acttgcttcg gttgcacacc ttgttgtgga tgaccagcct catcaagtgt 240ctaacgaata agtaaaacga ttgcagt 267 321 66 PRT Conus ammiralis 321 Met MetPhe Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 SerLeu Asn Ala Val Pro Leu Asp Gly Asp Gln Pro Ala Asp Gln Pro 20 25 30 AlaGlu Arg Leu Leu Asp Asp Ile Ser Ser Glu Asn Asn Pro Phe Tyr 35 40 45 AspPro Ala Lys Arg Cys Cys Met Thr Cys Phe Gly Cys Thr Pro Cys 50 55 60 CysGly 65 322 12 PRT Conus ammiralis PEPTIDE (1)..(12) Xaa at residue 10 isPro or Hyp 322 Cys Cys Met Thr Cys Phe Gly Cys Thr Xaa Cys Cys 1 5 10323 294 DNA Conus ammiralis 323 caagaaggat cgatagcagt tcatgatgtctaaactggga gccttgttga ccatctgtct 60 acttctgttt tcccttactg ctgttccgctggatggagat caacatgcag accaacctgc 120 agagcgtctg caggaccgcc ttccaactgaaaatcatccc ttatatgatc ccgtcaaacg 180 gtgttgcgat gattcggaat gcgactattcttgctggcct tgctgtattt tttcataacc 240 tttgttatcg cggcctcatc ctagtgtcaaatgaataagt aaaacgattg cagt 294 324 71 PRT Conus ammiralis 324 Met MetSer Lys Leu Gly Ala Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 SerLeu Thr Ala Val Pro Leu Asp Gly Asp Gln His Ala Asp Gln Pro 20 25 30 AlaGlu Arg Leu Gln Asp Arg Leu Pro Thr Glu Asn His Pro Leu Tyr 35 40 45 AspPro Val Lys Arg Cys Cys Asp Asp Ser Glu Cys Asp Tyr Ser Cys 50 55 60 TrpPro Cys Cys Ile Phe Ser 65 70 325 18 PRT Conus ammiralis PEPTIDE(1)..(18) Xaa at residue 6 is Glu or gamma-carboxy Glu; Xaa at residue13 is Pro or Hyp; Xaa at residue 12 is Trp or bromo-Trp; Xaa at residue9 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho-Tyr 325 Cys Cys Asp Asp Ser Xaa Cys Asp Xaa Ser Cys Xaa XaaCys Cys Ile 1 5 10 15 Phe Ser 326 284 DNA Conus ammiralis 326 caagagggatcgatagcagt tcatgatgtt taaactcgga gtcttgctga ccatctgtct 60 acttctgttttccctaattg ctgttccgct ggatggagat caacatgcag accaacctgc 120 agagcgtctgcaggaccgcc ttccaactga aaatcatccc ttatatgatc ccgtcaaacg 180 gtgttgcaggttgttatgcc tcagttgcaa cccttgttgt ggatgaccag ctttgttatc 240 acggcctcatcaagtgtcta atgaataagt aaaacgattg cagt 284 327 67 PRT Conus ammiralis 327Met Met Phe Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 1015 Ser Leu Ile Ala Val Pro Leu Asp Gly Asp Gln His Ala Asp Gln Pro 20 2530 Ala Glu Arg Leu Gln Asp Arg Leu Pro Thr Glu Asn His Pro Leu Tyr 35 4045 Asp Pro Val Lys Arg Cys Cys Arg Leu Leu Cys Leu Ser Cys Asn Pro 50 5560 Cys Cys Gly 65 328 13 PRT Conus ammiralis PEPTIDE (1)..(13) Xaa atresidue 11 is Pro or Hyp 328 Cys Cys Arg Leu Leu Cys Leu Ser Cys Asn XaaCys Cys 1 5 10 329 289 DNA Conus ammiralis 329 caagaaggat cgatagcagttcatgatgtc taaactggga gccttgttga ccatctgtct 60 acttctgttt tcccttactgctgttccgct ggatggagat caacatgcag accaacctgc 120 agagcgtctg caggaccgcattccaactga agatcatccc ttatttgatc ccaacaaacg 180 gtgttgcgat gattcggaatgcggctattc atgctggcct tgctgttatg gataagcttt 240 gttatcgcgg cctcatccagtgtcaacgaa taagtaaaac gattgcagt 289 330 70 PRT Conus ammiralis 330 MetMet Ser Lys Leu Gly Ala Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15Ser Leu Thr Ala Val Pro Leu Asp Gly Asp Gln His Ala Asp Gln Pro 20 25 30Ala Glu Arg Leu Gln Asp Arg Ile Pro Thr Glu Asp His Pro Leu Phe 35 40 45Asp Pro Asn Lys Arg Cys Cys Asp Asp Ser Glu Cys Gly Tyr Ser Cys 50 55 60Trp Pro Cys Cys Tyr Gly 65 70 331 16 PRT Conus ammiralis PEPTIDE(1)..(16) Xaa at residue6 is Glu or gamma-carboxy Glu; Xaa at residue 13is Pro or Hyp; Xaa at residue 12 is Trp or bromo-Trp; Xaa at residue 9and 16 is Tyr, 125I-Tyr, mono- iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho-Tyr 331 Cys Cys Asp Asp Ser Xaa Cys Gly Xaa Ser Cys Xaa XaaCys Cys Xaa 1 5 10 15 332 272 DNA Conus spurius 332 caagaaggatcgatagcagt tcatgatgtc taaactggga gtcttgctga ccatctgtct 60 gcttctgtttccacgtactt ctcttccgct ggatggagat caacctgcag tccgatctgc 120 aaagcgtatgcattcatcta tacagcgtcg tttctttgat cccgtcaaac ggtgttgccc 180 tagatgcagcgagtgcaacc cttgttgtgg atgaccagct ttgtcatcgc ggcctcatta 240 agtgtctaatgaataagtaa aatgattgca gt 272 333 63 PRT Conus spurius 333 Met Met SerLys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Pro ArgThr Ser Leu Pro Leu Asp Gly Asp Gln Pro Ala Val Arg Ser 20 25 30 Ala LysArg Met His Ser Ser Ile Gln Arg Arg Phe Phe Asp Pro Val 35 40 45 Lys ArgCys Cys Pro Arg Cys Ser Glu Cys Asn Pro Cys Cys Gly 50 55 60 334 12 PRTConus spurius PEPTIDE (1)..(12) Xaa at residue 7 is Glu or gamma-carboxyGlu; Xaa at residue 3 and 10 is Pro or Hyp 334 Cys Cys Xaa Arg Cys SerXaa Cys Asn Xaa Cys Cys 1 5 10 335 293 DNA Conus omaria 335 caagagggatcgatagcagt tcatgatgtc taaactggga gtctcgttga ccatctgtct 60 acttctattttcccttactg ctgttccgct tgatggagat caacatgcag accaacctgc 120 agagcgtctgcagggcgaca ttttatctga aaagcatccc ttatttaatc ccgtcaaacg 180 gtgttgcgatgaggaagaat gcagcagtgc atgctggcct tgttgttggg ggtgatcagc 240 tttgttatcgcggcctcatc aagtgtctaa tgaataagta aaatgattgc agt 293 336 70 PRT Conusomaria 336 Met Met Ser Lys Leu Gly Val Ser Leu Thr Ile Cys Leu Leu LeuPhe 1 5 10 15 Ser Leu Thr Ala Val Pro Leu Asp Gly Asp Gln His Ala AspGln Pro 20 25 30 Ala Glu Arg Leu Gln Gly Asp Ile Leu Ser Glu Lys His ProLeu Phe 35 40 45 Asn Pro Val Lys Arg Cys Cys Asp Glu Glu Glu Cys Ser SerAla Cys 50 55 60 Trp Pro Cys Cys Trp Gly 65 70 337 16 PRT Conus omariaPEPTIDE (1)..(16) Xaa at residue 4, 5 and 6 is Glu or gamma- carboxyGlu; Xaa at residue 13 is Pro or Hyp; Xaa at residue 12 and 16 is Trp orbromo-Trp 337 Cys Cys Asp Xaa Xaa Xaa Cys Ser Ser Ala Cys Xaa Xaa CysCys Xaa 1 5 10 15 338 293 DNA Conus omaria 338 caagaaggat cgatagcagttcatgatgtc taaactggga gtcttgttga tcatctgtct 60 acttctgtgt ccccttactgctgttctgga ggatggagat caacctgcag accgacctgc 120 agagcgtatg caggacgacatttcaactga gcatcatccc ttttatgatc ccgtcaaacg 180 gtgttgcaag tacgggtggacatgcttgct aggatgcact ccttgtgatt gttgaccagt 240 tttgttatcg cggcctcgtcaagtgtctaa tgaataagta aaacgattgc agt 293 339 70 PRT Conus omaria 339 MetMet Ser Lys Leu Gly Val Leu Leu Ile Ile Cys Leu Leu Leu Cys 1 5 10 15Pro Leu Thr Ala Val Leu Glu Asp Gly Asp Gln Pro Ala Asp Arg Pro 20 25 30Ala Glu Arg Met Gln Asp Asp Ile Ser Thr Glu His His Pro Phe Tyr 35 40 45Asp Pro Val Lys Arg Cys Cys Lys Tyr Gly Trp Thr Cys Leu Leu Gly 50 55 60Cys Thr Pro Cys Asp Cys 65 70 340 17 PRT Conus omaria PEPTIDE (1)..(17)Xaa at residue is 14 Pro or Hyp; Xaa at residue 6 is Trp or bromo-Trp;Xaa at residue 4 is Tyr, 125I-Tyr, mono- iodo-Tyr, di-iodo-Tyr,O-sulpho-Tyr or O-phospho-Tyr 340 Cys Cys Lys Xaa Gly Xaa Thr Cys LeuLeu Gly Cys Thr Xaa Cys Asp 1 5 10 15 Cys 341 290 DNA Conus omaria 341caagagggat cgatagcagt tcatgatgtc tatactggga gtcttgttga tcatctgtct 60acttctgtgt ccccttactg ctgttctgga ggatggagat caacctgcag accgacctgc 120agagcgtatg caggacggca tttcatctga acatcatccc tttttggatc ccgtcaaacg 180gtgttgccat ctattggcat gccgctttgg atgctcgcct tgttgttggt gaccagcttt 240gttatcgcgg cctcatcaag tgtctaatga ataagtaaaa cgattgcagt 290 342 69 PRTConus omaria 342 Met Met Ser Ile Leu Gly Val Leu Leu Ile Ile Cys Leu LeuLeu Cys 1 5 10 15 Pro Leu Thr Ala Val Leu Glu Asp Gly Asp Gln Pro AlaAsp Arg Pro 20 25 30 Ala Glu Arg Met Gln Asp Gly Ile Ser Ser Glu His HisPro Phe Leu 35 40 45 Asp Pro Val Lys Arg Cys Cys His Leu Leu Ala Cys ArgPhe Gly Cys 50 55 60 Ser Pro Cys Cys Trp 65 343 16 PRT Conus omariaPEPTIDE (1)..(16) Xaa at residue 13 is Pro or Hyp; Xaa at residue 16 isTrp or bromo-Trp 343 Cys Cys His Leu Leu Ala Cys Arg Phe Gly Cys Ser XaaCys Cys Xaa 1 5 10 15 344 293 DNA Conus omaria 344 caagaaggat cgatagcagttcatgatgtc taaactggga gtcttgttga tcatctgtct 60 acttctttgt ccccttactgctgttccgca ggatggagat caacctgcag accgacctgc 120 agagcgtatg cagggcggcatttcatctga acatcatccc ttttttgatc ccgtcaaacg 180 gtgttgcagg tacgggtggacatgctggct aggatgcact ccctgtggtt gttgaccagc 240 tttgttatcg cggcctcatcaagtgtctaa tgaataagta aaacgattgc agt 293 345 70 PRT Conus omaria 345 MetMet Ser Lys Leu Gly Val Leu Leu Ile Ile Cys Leu Leu Leu Cys 1 5 10 15Pro Leu Thr Ala Val Pro Gln Asp Gly Asp Gln Pro Ala Asp Arg Pro 20 25 30Ala Glu Arg Met Gln Gly Gly Ile Ser Ser Glu His His Pro Phe Phe 35 40 45Asp Pro Val Lys Arg Cys Cys Arg Tyr Gly Trp Thr Cys Trp Leu Gly 50 55 60Cys Thr Pro Cys Gly Cys 65 70 346 17 PRT Conus omaria PEPTIDE (1)..(17)Xaa at residue 14 is Pro or Hyp; Xaa at residue 6 and 9 is Trp orbromo-Trp; Xaa at residue 4 is Tyr, 125I-Tyr, mono-iodo-Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 346 Cys Cys Arg Xaa Gly XaaThr Cys Xaa Leu Gly Cys Thr Xaa Cys Gly 1 5 10 15 Cys 347 293 DNA Conusepiscopatus 347 caagaaggat cgatagcagt tcatgatgtc taaactggga gtcttgttgaccatctgtct 60 acttctgttt tcccttattg ctgttccgct tgatggagat caacatgcagaccaacctgc 120 agagcgtctg cagggcgaca ttttatctga aaagcatccc ttatttatgcctgtcaaacg 180 gtgttgcgat gaggacgaat gcaacagttc atgctggcct tgttgttgggggtgatcagc 240 tttgttatcg cggcctgatc aagtgtataa tgaataagta aaacgattgcagt 293 348 70 PRT Conus episcopatus 348 Met Met Ser Lys Leu Gly Val LeuLeu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Ser Leu Ile Ala Val Pro LeuAsp Gly Asp Gln His Ala Asp Gln Pro 20 25 30 Ala Glu Arg Leu Gln Gly AspIle Leu Ser Glu Lys His Pro Leu Phe 35 40 45 Met Pro Val Lys Arg Cys CysAsp Glu Asp Glu Cys Asn Ser Ser Cys 50 55 60 Trp Pro Cys Cys Trp Gly 6570 349 16 PRT Conus episcopatus PEPTIDE (1)..(16) Xaa at residue 4 and 6is Glu or gamma-carboxy Glu; Xaa at residue 13 is Pro or Hyp; Xaa atresidue 12 and 16 is Trp or bromo-Trp 349 Cys Cys Asp Xaa Asp Xaa CysAsn Ser Ser Cys Xaa Xaa Cys Cys Xaa 1 5 10 15 350 293 DNA Conusepiscopatus 350 caagagggat cgatagcagt tcatgatgtc taaactggga gtcttgttgaccatctgtct 60 acttctgttt tcccttattg ctgttccgct tgatggagat caacatgcagaccaacctgc 120 agagcgtctg cagggcgaca ttttatctga aaagcatccc ttatttatgcctgtcaaacg 180 gtgttgcgat gaggacgaat gcagcagttc atgctggcct tgttgttggggatgagcagc 240 tttgttatcg cggcctcatc aagtgtctaa tgaataagta aaacgattgcagt 293 351 70 PRT Conus episcopatus 351 Met Met Ser Lys Leu Gly Val LeuLeu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Ser Leu Ile Ala Val Pro LeuAsp Gly Asp Gln His Ala Asp Gln Pro 20 25 30 Ala Glu Arg Leu Gln Gly AspIle Leu Ser Glu Lys His Pro Leu Phe 35 40 45 Met Pro Val Lys Arg Cys CysAsp Glu Asp Glu Cys Ser Ser Ser Cys 50 55 60 Trp Pro Cys Cys Trp Gly 6570 352 16 PRT Conus episcopatus PEPTIDE (1)..(16) Xaa at residue4 and 6is Glu or gamma-carboxy Glu; Xaa at residue 13 is Pro or Hyp; Xaa atresidue 12 and 16 is Trp or bromo-Trp 352 Cys Cys Asp Xaa Asp Xaa CysSer Ser Ser Cys Xaa Xaa Cys Cys Xaa 1 5 10 15 353 290 DNA Conusepiscopatus 353 caagagggat cgatagcagt tcatgatgtc taaactggga gtcttgttgaccatctgtct 60 acttctgttt tcccttactg ctgttccgct tgatggagat caacatgcagaccaacctgc 120 agagcgtctg cagggcgaca ttttatctga aaagcatccc ttatttaatcccgtcaaacg 180 gtgttgcccg gcggcggcat gtgccatggg atgcaagcct tgttgtggatgagcagcttt 240 gttatcgtgg cctcatcaag tgtctaatga ataagtaaaa cgattgcagt290 354 69 PRT Conus episcopatus 354 Met Met Ser Lys Leu Gly Val Leu LeuThr Ile Cys Leu Leu Leu Phe 1 5 10 15 Ser Leu Thr Ala Val Pro Leu AspGly Asp Gln His Ala Asp Gln Pro 20 25 30 Ala Glu Arg Leu Gln Gly Asp IleLeu Ser Glu Lys His Pro Leu Phe 35 40 45 Asn Pro Val Lys Arg Cys Cys ProAla Ala Ala Cys Ala Met Gly Cys 50 55 60 Lys Pro Cys Cys Gly 65 355 15PRT Conus episcopatus PEPTIDE (1)..(15) Xaa at residue 3 and 13 is Proor Hyp 355 Cys Cys Xaa Ala Ala Ala Cys Ala Met Gly Cys Lys Xaa Cys Cys 15 10 15 356 295 DNA Conus aulicus 356 caagagggat cgatagcagt tcatgatgtctaaactggga gtcttgttga ccatctgtct 60 gcttctgttt tccgttactg ctcttccgccggatggagat caacctgcag accgagctgc 120 agagcgtagg caggtcgagc agcatcccgtgtttgatcat gaaagagggt gttgctcgcc 180 accatgccac agtatttgcg ctgctttctgttgcgggtga tgataacgtg ttgatgaccc 240 actttgtcat cacggctgcg tcaagtgtctaatgaataag taaaatgatt gcagt 295 357 65 PRT Conus aulicus 357 Met Met SerLys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Ser ValThr Ala Leu Pro Pro Asp Gly Asp Gln Pro Ala Asp Arg Ala 20 25 30 Ala GluArg Arg Gln Val Glu Gln His Pro Val Phe Asp His Glu Arg 35 40 45 Gly CysCys Ser Pro Pro Cys His Ser Ile Cys Ala Ala Phe Cys Cys 50 55 60 Gly 65358 16 PRT Conus aulicus PEPTIDE (1)..(16) Xaa at residue 5 and 6 is Proor Hyp 358 Gly Cys Cys Ser Xaa Xaa Cys His Ser Ile Cys Ala Ala Phe CysCys 1 5 10 15 359 290 DNA Conus aulicus 359 caagagggat cgatagcagttcatgatgtc taaactggga gtcttgttga ccatctgtct 60 acttctgttt tcccttactgctgttccgct tgatggagat caacatgcag accaacctgc 120 agagcgtctg cagggcgacattttatctga aaagcatccc ttatttaatc ccgtcaaacg 180 gtgttgccga ccggtggcatgtgccatggg atgcaagcct tgttgtggat gagcagcttt 240 gttatcgtgg cctcatcaagtgtctaatga ataagtaaaa tgattgcagt 290 360 69 PRT Conus aulicus 360 MetMet Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15Ser Leu Thr Ala Val Pro Leu Asp Gly Asp Gln His Ala Asp Gln Pro 20 25 30Ala Glu Arg Leu Gln Gly Asp Ile Leu Ser Glu Lys His Pro Leu Phe 35 40 45Asn Pro Val Lys Arg Cys Cys Arg Pro Val Ala Cys Ala Met Gly Cys 50 55 60Lys Pro Cys Cys Gly 65 361 15 PRT Conus aulicus PEPTIDE (1)..(15) Xaa atresidue 4 and 13 is Pro or Hyp 361 Cys Cys Arg Xaa Val Ala Cys Ala MetGly Cys Lys Xaa Cys Cys 1 5 10 15 362 290 DNA Conus aulicus 362caagagggat cgatagcagt tcatgatgtc taaactggga gtcttgttga tcatctgtct 60acttctgtct ccccttactg ctgttccgct ggatggagat caacctgcag accgacctgc 120agagcgtatg caggacgaca tttcatctga acatcaaccc atgtttgatg ccatcagaca 180gtgttgcccg gcggtggcat gcgccatggg atgcgagcct tgttgtggat gaccagcttt 240gttatcgcgg cctcatcaag tgtctaatga ataagtaaaa tgattgcagt 290 363 69 PRTConus aulicus 363 Met Met Ser Lys Leu Gly Val Leu Leu Ile Ile Cys LeuLeu Leu Ser 1 5 10 15 Pro Leu Thr Ala Val Pro Leu Asp Gly Asp Gln ProAla Asp Arg Pro 20 25 30 Ala Glu Arg Met Gln Asp Asp Ile Ser Ser Glu HisGln Pro Met Phe 35 40 45 Asp Ala Ile Arg Gln Cys Cys Pro Ala Val Ala CysAla Met Gly Cys 50 55 60 Glu Pro Cys Cys Gly 65 364 16 PRT Conus aulicusPEPTIDE (1)..(16) Xaa at residue 1 is Gln or pyro-Glu; Xaa at residue 13is Glu or gamma-carboxy Glu; Xaa at residue 4 and 14 is Pro or Hyp 364Xaa Cys Cys Xaa Ala Val Ala Cys Ala Met Gly Cys Xaa Xaa Cys Cys 1 5 1015 365 293 DNA Conus aureus 365 caagaaggat cgatagcagt tcatgatgtctaaactggga gccttgttga ccatctgtct 60 acttctgttt tcccttactg ctgttccgctggatggagat caacatgcag accaacatgc 120 agagcgtctg catgaccgcc ttccaactgaaaatcatccc ttatatgatc ccgtcaaacg 180 gtgttgcgat gattcggaat gcgactattcttgctggcct tgctgtattt ttggataacc 240 tttgttatcg cggcctcatc aagtgtcaaatgaataagta aaacgattgc agt 293 366 71 PRT Conus aureus 366 Met Met SerLys Leu Gly Ala Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Ser LeuThr Ala Val Pro Leu Asp Gly Asp Gln His Ala Asp Gln His 20 25 30 Ala GluArg Leu His Asp Arg Leu Pro Thr Glu Asn His Pro Leu Tyr 35 40 45 Asp ProVal Lys Arg Cys Cys Asp Asp Ser Glu Cys Asp Tyr Ser Cys 50 55 60 Trp ProCys Cys Ile Phe Gly 65 70 367 17 PRT Conus aureus PEPTIDE (1)..(17) Xaaat residue 6 is Glu or gamma-carboxy Glu; Xaa at residue 13 is Pro orHyp; Xaa at residue 12 is Trp or bromo -Trp; Xaa at residue 9 is Tyr,125I-Tyr, mono-iodo-Tyr, di-iodo- Tyr, O-sulpho-Tyr or O-phospho-Tyr 367Cys Cys Asp Asp Ser Xaa Cys Asp Xaa Ser Cys Xaa Xaa Cys Cys Ile 1 5 1015 Phe 368 290 DNA Conus aureus 368 caagagggat cgatagcagt tcatgatgtctaaactggga gccttgttga ccatctgtct 60 acttctgttt tccctaactg ctgttccgctggatggagat caacatgcag accaacctgc 120 agagcgtctg caggaccgca ttccaactgaaaatcatccc ttatttgatc cgaacaaacg 180 gtgttgcaat gattgggaat gcgacgattcatgctggcct tgctgttatg gataaccttt 240 gttatcgcgg cctcatcaag tgtcaaatgaataagtaaaa cgattgcagt 290 369 70 PRT Conus aureus 369 Met Met Ser LysLeu Gly Ala Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 Ser Leu ThrAla Val Pro Leu Asp Gly Asp Gln His Ala Asp Gln Pro 20 25 30 Ala Glu ArgLeu Gln Asp Arg Ile Pro Thr Glu Asn His Pro Leu Phe 35 40 45 Asp Pro AsnLys Arg Cys Cys Asn Asp Trp Glu Cys Asp Asp Ser Cys 50 55 60 Trp Pro CysCys Tyr Gly 65 70 370 16 PRT Conus aureus PEPTIDE (1)..(16) Xaa atresidue 6 is Glu or gamma-carboxy Glu; Xaa at residue 13 is Pro or Hyp;Xaa at residue 5 and 12 is Trp or bromo-Trp; Xaa at residue 16 is Tyr,125I-Tyr, mono-iodo- Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 370Cys Cys Asn Asp Xaa Xaa Cys Asp Asp Ser Cys Xaa Xaa Cys Cys Xaa 1 5 1015 371 310 DNA Conus consors 371 caagagggat cgatagcagt tcatgatgtctaaactggga gtcttgttga ccatctgttt 60 gcttctgttt ccccttactg ctcttccaatggatggagat caatctgtag accgacctgc 120 agagcgtatg caggacgaca tttcatctgagctgcatccc ttgttcaatc agaaaagaat 180 gtgttgcggc gaaggtgcgc catgccccagctatttcaga aacagtcaga tttgtcattg 240 ttgttaaatg acaacgtgtc gatgaccaacttcgttatca cgactaatga ataagtaaaa 300 tgattgcagt 310 372 74 PRT Conusconsors 372 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu LeuPhe 1 5 10 15 Pro Leu Thr Ala Leu Pro Met Asp Gly Asp Gln Ser Val AspArg Pro 20 25 30 Ala Glu Arg Met Gln Asp Asp Ile Ser Ser Glu Leu His ProLeu Phe 35 40 45 Asn Gln Lys Arg Met Cys Cys Gly Glu Gly Ala Pro Cys ProSer Tyr 50 55 60 Phe Arg Asn Ser Gln Ile Cys His Cys Cys 65 70 373 22PRT Conus consors PEPTIDE (1)..(22) Xaa at residue 5 is Glu orgamma-carboxy Glu; Xaa at residue 8 and 10 is Pro or Hyp; Xaa at residue12 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho-Tyr 373 Met Cys Cys Gly Xaa Gly Ala Xaa Cys Xaa Ser Xaa PheArg Asn Ser 1 5 10 15 Gln Ile Cys His Cys Cys 20 374 315 DNA Conusconsors 374 taagagggat cgatagcagt tcatgatgtc taaactggga gtcttgttgaccatctgtct 60 gcttctgttt ccccttattg ctcttccaat ggatggagat caacctgcagaccgacctgc 120 agagcgtatg caggacgaca tttcatctca gcagcatccc ttgtttgataagagaggccg 180 ctgttgcgat gtgccgaacg catgctccgg cagatggtgc agagatcacgcacaatgttg 240 cggatgacga taacgtgttg atgaccaact ttgtgatcac ggctacatcaagtgaataag 300 taaaacgatt gcagt 315 375 74 PRT Conus consors 375 Met MetSer Lys Leu Gly Val Leu Leu Thr Ile Cys Leu Leu Leu Phe 1 5 10 15 ProLeu Ile Ala Leu Pro Met Asp Gly Asp Gln Pro Ala Asp Arg Pro 20 25 30 AlaGlu Arg Met Gln Asp Asp Ile Ser Ser Gln Gln His Pro Leu Phe 35 40 45 AspLys Arg Gly Arg Cys Cys Asp Val Pro Asn Ala Cys Ser Gly Arg 50 55 60 TrpCys Arg Asp His Ala Gln Cys Cys Gly 65 70 376 22 PRT Conus consorsPEPTIDE (1)..(22) Xaa at residue 7 is Pro or Hyp; Xaa at residue 14 isTrp or bromo -Trp 376 Gly Arg Cys Cys Asp Val Xaa Asn Ala Cys Ser GlyArg Xaa Cys Arg 1 5 10 15 Asp His Ala Gln Cys Cys 20 377 322 DNA Conusconsors 377 caagagggat cgatagcagt tcatgatgtc taaactggga gtcttgttgactgtctgttt 60 gcttctgttt ccccttactg ctcttccgat ggatggagat caacctgcagaccaacctgc 120 agagcgtatg caggacgaca tttcatctga gcagcatccc ttgtttgataagagacaaag 180 gtgttgcact gggaagaagg ggtcatgctc cggtaaagca tgcaaaagtctcaaatgttg 240 ctctggacga taacgtgttg atgaccaact ttgttatcac ggctacgtcaagtgtctagt 300 gaataagtaa aacgattgca gt 322 378 76 PRT Conus consors 378Met Met Ser Lys Leu Gly Val Leu Leu Thr Val Cys Leu Leu Leu Phe 1 5 1015 Pro Leu Thr Ala Leu Pro Met Asp Gly Asp Gln Pro Ala Asp Gln Pro 20 2530 Ala Glu Arg Met Gln Asp Asp Ile Ser Ser Glu Gln His Pro Leu Phe 35 4045 Asp Lys Arg Gln Arg Cys Cys Thr Gly Lys Lys Gly Ser Cys Ser Gly 50 5560 Lys Ala Cys Lys Ser Leu Lys Cys Cys Ser Gly Arg 65 70 75 379 23 PRTConus consors PEPTIDE (1)..(23) Xaa at residue 1 is Gln or pyro-Glu 379Xaa Arg Cys Cys Thr Gly Lys Lys Gly Ser Cys Ser Gly Lys Ala Cys 1 5 1015 Lys Ser Leu Lys Cys Cys Ser 20 380 284 DNA Conus emaciatus 380caagagggat cgatagcagt tcatgatgtc taaactggga gtcttgctga ccatctgtct 60gcttctgttt ccccttactg ttcttccgat ggatggagat caacctgcag acctacctgc 120attgcgtgcg cagttctttg cacctgaaca tagtccccgg tttgaccccg tcaaacggtg 180ctgctcgcgg gattgcagtg tttgcatccc ttgttgcccg tatggatcac cttgattatt 240gcggccacgt caagtgtcta atgaataagt aaaatgattg cagt 284 381 70 PRT Conusemaciatus 381 Met Met Ser Lys Leu Gly Val Leu Leu Thr Ile Cys Leu LeuLeu Phe 1 5 10 15 Pro Leu Thr Val Leu Pro Met Asp Gly Asp Gln Pro AlaAsp Leu Pro 20 25 30 Ala Leu Arg Ala Gln Phe Phe Ala Pro Glu His Ser ProArg Phe Asp 35 40 45 Pro Val Lys Arg Cys Cys Ser Arg Asp Cys Ser Val CysIle Pro Cys 50 55 60 Cys Pro Tyr Gly Ser Pro 65 70 382 18 PRT Conusemaciatus PEPTIDE (1)..(18) Xaa at residue 11, 14 and 18 is Pro or Hyp;Xaa at residue 15 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr,O-sulpho-Tyr or O-phospho-Tyr 382 Cys Cys Ser Arg Asp Cys Ser Val CysIle Xaa Cys Cys Xaa Xaa Gly 1 5 10 15 Ser Xaa 383 13 PRT Conusaurisiacus 383 Cys Cys Lys Val Gln Cys Glu Ser Cys Thr Pro Cys Cys 1 510 384 15 PRT Conus atlanticus 384 Cys Cys Glu Leu Pro Cys Gly Pro GlyPhe Cys Val Pro Cys Cys 1 5 10 15 385 14 PRT Conus arentus 385 Cys CysGlu Arg Pro Cys Asn Ile Gly Cys Val Pro Cys Cys 1 5 10 386 16 PRT Conusbandus 386 Cys Cys Asn Trp Pro Cys Ser Met Gly Cys Ile Pro Cys Cys TyrTyr 1 5 10 15 387 15 PRT Conus betulinus 387 Cys Cys Glu Leu Pro Cys HisGly Cys Val Pro Cys Cys Trp Pro 1 5 10 15 388 16 PRT Conus betulinus 388Cys Cys Gly Leu Pro Cys Asn Gly Cys Val Pro Cys Cys Trp Pro Ser 1 5 1015 389 18 PRT Conus betulinus 389 Cys Cys Ser Arg Asn Cys Ala Val CysIle Pro Cys Cys Pro Asn Trp 1 5 10 15 Pro Ala 390 14 PRT Conus betulinus390 Cys Cys Lys Gln Ser Cys Thr Thr Cys Met Pro Cys Cys Trp 1 5 10 39114 PRT Conus betulinus PEPTIDE (1)..(14) Xaa is Glu or gamma-carboxy Glu391 Ala Cys Cys Xaa Gln Ser Cys Thr Thr Cys Met Pro Cys Cys 1 5 10 39214 PRT Conus betulinus 392 Cys Cys Glu Gln Ser Cys Thr Thr Cys Met ProCys Cys Trp 1 5 10 393 18 PRT Conus caracteristicus 393 Arg Cys Cys ArgTyr Pro Cys Pro Asp Ser Cys His Gly Ser Cys Cys 1 5 10 15 Tyr Lys 394 15PRT Conus caracteristicus 394 Cys Cys Pro Pro Val Ala Cys Asn Met GlyCys Lys Pro Cys Cys 1 5 10 15 395 17 PRT Conus caracteristicus 395 CysCys Asp Asp Ser Glu Cys Asp Tyr Ser Cys Trp Pro Cys Cys Met 1 5 10 15Phe 396 14 PRT Conus caracteristicus 396 Cys Cys Arg Arg Cys Tyr Met GlyCys Ile Pro Cys Cys Phe 1 5 10 397 16 PRT Conus textile 397 Cys Cys ProPro Val Ala Cys Asn Met Gly Cys Lys Pro Cys Cys Gly 1 5 10 15 398 19 PRTConus marmoreus PEPTIDE (1)..(19) Xaa is Hyp 398 Ser Lys Gln Cys Cys HisLeu Ala Ala Cys Arg Phe Gly Cys Thr Xaa 1 5 10 15 Cys Cys Asn 399 15 PRTConus capitaneus 399 Ser Cys Cys Arg Asp Cys Gly Glu Asp Cys Val Gly CysCys Arg 1 5 10 15 400 16 PRT Conus coronatus 400 Cys Cys Asp Trp Pro CysIle Pro Gly Cys Thr Pro Cys Cys Leu Pro 1 5 10 15 401 18 PRT Conus dalli401 Cys Cys Asp Asp Ser Glu Cys Asp Tyr Ser Cys Trp Pro Cys Cys Ile 1 510 15 Leu Ser 402 17 PRT Conus dalli 402 Glx Gln Cys Cys Pro Pro Val AlaCys Asn Met Gly Cys Glu Pro Cys 1 5 10 15 Cys 403 16 PRT Conus dalli 403Cys Cys Asn Ala Gly Phe Cys Arg Phe Gly Cys Thr Pro Cys Cys Trp 1 5 1015 404 14 PRT Conus distans 404 Glx Cys Cys Val His Pro Cys Pro Cys ThrPro Cys Cys Arg 1 5 10 405 14 PRT Conus figulinus 405 Cys Cys Pro TrpPro Cys Asn Ile Gly Cys Val Pro Cys Cys 1 5 10 406 14 PRT Conusfigulinus 406 Cys Cys Ser Lys Asn Cys Ala Val Cys Ile Pro Cys Cys Pro 15 10 407 15 PRT Conus figulinus 407 Cys Cys Arg Trp Pro Cys Pro Ala ArgCys Gly Ser Cys Cys Leu 1 5 10 15 408 16 PRT Conus figulinus 408 Cys CysGlu Leu Ser Arg Cys Leu Gly Cys Val Pro Cys Cys Thr Ser 1 5 10 15 409 16PRT Conus figulinus 409 Cys Cys Glu Leu Ser Lys Cys His Gly Cys Val ProCys Cys Ile Pro 1 5 10 15 410 16 PRT Conus generalis 410 Glx Cys Cys ThrPhe Cys Asn Phe Gly Cys Gln Pro Cys Cys Val Pro 1 5 10 15 411 16 PRTConus generalis 411 Glx Cys Cys Thr Phe Cys Asn Phe Gly Cys Gln Pro CysCys Leu Thr 1 5 10 15 412 16 PRT Conus generalis 412 Glx Cys Cys Thr PheCys Asn Phe Gly Cys Gln Pro Cys Cys Val Pro 1 5 10 15 413 17 PRT Conusgloriamaris 413 Cys Cys Asp Asp Ser Glu Cys Asp Tyr Ser Cys Trp Pro CysCys Met 1 5 10 15 Phe 414 17 PRT Conus gloriamaris 414 Gly Cys Cys HisLeu Leu Ala Cys Arg Phe Gly Cys Ser Pro Cys Cys 1 5 10 15 Trp 415 16 PRTConus gloriamaris 415 Cys Cys Ser Trp Asp Val Cys Asp His Pro Ser CysThr Cys Cys Gly 1 5 10 15 416 13 PRT Conus laterculatus 416 Cys Cys AspTrp Pro Cys Ser Gly Cys Ile Pro Cys Cys 1 5 10 417 19 PRT Conusleopardus 417 Glx Ile Asn Cys Cys Pro Trp Pro Cys Pro Ser Thr Cys ArgHis Gln 1 5 10 15 Cys Cys His 418 19 PRT Conus lividus 418 Glx Ile AsnCys Cys Pro Trp Pro Cys Pro Asp Ser Cys His Tyr Gln 1 5 10 15 Cys CysHis 419 14 PRT Conus marmoreus 419 Cys Cys Arg Leu Ser Cys Gly Leu GlyCys His Pro Cys Cys 1 5 10 420 17 PRT Conus marmoreus 420 Glu Cys CysGly Ser Phe Ala Cys Arg Phe Gly Cys Val Pro Cys Cys 1 5 10 15 Val 421 19PRT Conus marmoreus 421 Ser Lys Gln Cys Cys His Leu Pro Ala Cys Arg PheGly Cys Thr Pro 1 5 10 15 Cys Cys Trp 422 17 PRT Conus marmoreus 422 MetGly Cys Cys Pro Phe Pro Cys Lys Thr Ser Cys Thr Thr Leu Cys 1 5 10 15Cys 423 14 PRT Conus musicus 423 Ala Cys Cys Glu Gln Ser Cys Thr Thr CysPhe Pro Cys Cys 1 5 10 424 15 PRT Conus nobilis 424 Cys Cys Glu Leu ProCys Gly Pro Gly Phe Cys Val Pro Cys Cys 1 5 10 15 425 14 PRT Conuspulicarius 425 Cys Cys Asn Ser Cys Tyr Met Gly Cys Ile Pro Cys Cys Phe 15 10 426 17 PRT Conus quercinus 426 Glx Arg Cys Cys Gln Trp Pro Cys ProGly Ser Cys Arg Cys Cys Arg 1 5 10 15 Thr 427 18 PRT Conus quercinus 427Glx Arg Cys Cys Arg Trp Pro Cys Pro Gly Ser Cys Arg Cys Cys Arg 1 5 1015 Tyr Arg 428 18 PRT Conus quercinus 428 Arg Cys Cys Arg Tyr Pro CysPro Asp Ser Cys His Gly Ser Cys Cys 1 5 10 15 Tyr Lys 429 15 PRT Conusquercinus PEPTIDE (1)..(15) Xaa is Hyp 429 Cys Cys Ser Gln Asp Cys LeuVal Cys Ile Xaa Cys Cys Pro Asn 1 5 10 15 430 15 PRT Conus quercinusPEPTIDE (1)..(15) Xaa is Hyp 430 Cys Cys Ser Arg His Cys Trp Val Cys IleXaa Cys Cys Pro Asn 1 5 10 15 431 16 PRT Conus rattus 431 Glx Thr CysCys Ser Asn Cys Gly Glu Asp Cys Asp Gly Cys Cys Gln 1 5 10 15 432 20 PRTConus striatus 432 Glx Asn Cys Cys Asn Gly Gly Cys Ser Ser Lys Trp CysArg Asp His 1 5 10 15 Ala Arg Cys Cys 20 433 12 PRT Conus textilePEPTIDE (1)..(12) Xaa is Hyp 433 Cys Cys Arg Thr Cys Phe Gly Cys Thr XaaCys Cys 1 5 10 434 14 PRT Conus tessulatus 434 Cys Cys His Lys Cys TyrMet Gly Cys Ile Pro Cys Cys Ile 1 5 10 435 18 PRT Conus tessulatus 435Lys Cys Cys Arg Pro Pro Cys Ala Met Ser Cys Gly Met Ala Arg Cys 1 5 1015 Cys Tyr 436 23 PRT Conus betulinus 436 Arg Cys Cys Arg Trp Pro CysPro Ser Ile Cys Gly Met Ala Arg Cys 1 5 10 15 Cys Phe Val Met Ile ThrCys 20 437 23 PRT Conus betulinus 437 Arg Cys Cys Arg Trp Pro Cys ProSer Arg Cys Gly Met Ala Arg Cys 1 5 10 15 Cys Phe Val Met Ile Thr Cys 20438 15 PRT Conus textile 438 Phe Cys Cys Asp Ser Asn Trp Cys His Asp CysGlu Cys Cys Tyr 1 5 10 15 439 16 PRT Conus marmoreus 439 Cys Cys His TrpAsn Trp Cys Asp His Leu Cys Ser Cys Cys Gly Ser 1 5 10 15 440 16 PRTConus marmoreus PEPTIDE (1)..(16) Xaa is Hyp 440 Asp Cys Cys Xaa Leu ProAla Cys Pro Phe Gly Cys Asn Xaa Cys Cys 1 5 10 15 441 16 PRT Conusmarmoreus PEPTIDE (1)..(16) Xaa is Hyp 441 Cys Cys Ala Pro Ser Ala CysArg Leu Gly Cys Arg Xaa Cys Cys Arg 1 5 10 15 442 16 PRT Conus marmoreusPEPTIDE (1)..(16) Xaa is Hyp 442 Cys Cys Ala Xaa Ser Ala Cys Arg Leu GlyCys Arg Xaa Cys Cys Arg 1 5 10 15 443 16 PRT Conus marmoreus 443 Cys CysAla Pro Ser Ala Cys Arg Leu Gly Cys Arg Pro Cys Cys Arg 1 5 10 15 444 17PRT Conus marmoreus PEPTIDE (1)..(17) Xaa is Hyp 444 Gly Cys Cys Gly SerPhe Ala Cys Arg Phe Gly Cys Val Xaa Cys Cys 1 5 10 15 Val 445 15 PRTConus textile 445 Cys Cys Ser Trp Asp Val Cys Asp His Pro Ser Cys ThrCys Cys 1 5 10 15 446 16 PRT Conus textile 446 Arg Cys Cys Lys Phe ProCys Pro Asp Ser Cys Arg Tyr Leu Cys Cys 1 5 10 15 447 17 PRT Conusaureus 447 Cys Cys Asp Asp Ser Glu Cys Asp Tyr Ser Cys Trp Pro Cys CysIle 1 5 10 15 Phe 448 16 PRT Conus aureus 448 Cys Cys Asn Asp Trp GluCys Asp Asp Ser Cys Trp Pro Cys Cys Tyr 1 5 10 15 449 16 PRT Conusammiralis 449 Arg Cys Cys Arg Phe Pro Cys Pro Asp Thr Cys Arg His LeuCys Cys 1 5 10 15 450 12 PRT Conus ammiralis 450 Cys Cys Met Thr Cys PheGly Cys Thr Pro Cys Cys 1 5 10 451 18 PRT Conus ammiralis 451 Cys CysAsp Asp Ser Glu Cys Asp Tyr Ser Cys Trp Pro Cys Cys Ile 1 5 10 15 PheSer 452 13 PRT Conus ammiralis 452 Cys Cys Arg Leu Leu Cys Leu Ser CysAsn Pro Cys Cys 1 5 10 453 16 PRT Conus ammiralis 453 Cys Cys Asp AspSer Glu Cys Gly Tyr Ser Cys Trp Pro Cys Cys Tyr 1 5 10 15 454 16 PRTConus aulicus 454 Gly Cys Cys Ser Pro Pro Cys His Ser Ile Cys Ala AlaPhe Cys Cys 1 5 10 15 455 15 PRT Conus aulicus 455 Cys Cys Arg Pro ValAla Cys Ala Met Gly Cys Lys Pro Cys Cys 1 5 10 15 456 16 PRT Conusaulicus 456 Glx Cys Cys Pro Ala Val Ala Cys Ala Met Gly Cys Glu Pro CysCys 1 5 10 15 457 18 PRT Conus emaciatus 457 Cys Cys Ser Arg Asp Cys SerVal Cys Ile Pro Cys Cys Pro Tyr Gly 1 5 10 15 Ser Pro 458 16 PRT Conusepiscopatus 458 Cys Cys Asp Glu Asp Glu Cys Asn Ser Ser Cys Trp Pro CysCys Trp 1 5 10 15 459 16 PRT Conus episcopatus 459 Cys Cys Asp Glu AspGlu Cys Ser Ser Ser Cys Trp Pro Cys Cys Trp 1 5 10 15 460 15 PRT Conusepiscopatus 460 Cys Cys Pro Ala Ala Ala Cys Ala Met Gly Cys Lys Pro CysCys 1 5 10 15 461 16 PRT Conus omaria 461 Cys Cys Asp Glu Glu Glu CysSer Ser Ala Cys Trp Pro Cys Cys Trp 1 5 10 15 462 16 PRT Conus omaria462 Cys Cys His Leu Leu Ala Cys Arg Phe Gly Cys Ser Pro Cys Cys Trp 1 510 15 463 12 PRT Conus spurius 463 Cys Cys Pro Arg Cys Ser Glu Cys AsnPro Cys Cys 1 5 10 464 16 PRT Conus pennaceus 464 Arg Cys Cys Lys PhePro Cys Pro Asp Ser Cys Lys Tyr Leu Cys Cys 1 5 10 15 465 19 PRT Conusflavidus 465 Arg Cys Cys Arg Trp Pro Cys Pro Ser Ile Cys Gly Met Ala ArgCys 1 5 10 15 Cys Ser Ser 466 14 PRT Conus pulicarius 466 Cys Cys LysLeu Leu Cys Gly Cys Thr Pro Cys Cys His Ile 1 5 10 467 15 PRT Conusebraceus 467 Cys Cys Glu Gln Pro Cys Tyr Met Gly Cys Ile Pro Cys Cys Phe1 5 10 15 468 15 PRT Conus ebraceus 468 Cys Cys Ala Gln Pro Cys Tyr MetGly Cys Ile Pro Cys Cys Phe 1 5 10 15 469 14 PRT Conus pulicarius 469Cys Cys Val Ser Cys Tyr Met Gly Cys Ile Pro Cys Cys Phe 1 5 10 470 16PRT Conus miliaris 470 Cys Cys Asp Trp Pro Cys Ser Ala Gly Cys Tyr ProCys Cys Phe Pro 1 5 10 15 471 16 PRT Conus miliaris 471 Gly Cys Cys ProPro Met Cys Thr Pro Cys Phe Pro Cys Cys Phe Arg 1 5 10 15 472 23 PRTConus rattus 472 Arg Gly Cys Cys Ala Pro Pro Arg Lys Cys Lys Asp Arg AlaCys Lys 1 5 10 15 Pro Ala Arg Cys Cys Gly Pro 20 473 22 PRT Conusstercusmuscarum 473 Glx Arg Cys Cys Asn Gly Arg Arg Gly Cys Ser Ser ArgTrp Cys Arg 1 5 10 15 Asp His Ser Arg Cys Cys 20 474 22 PRT Conusconsors 474 Gly Arg Cys Cys Asp Val Pro Asn Ala Cys Ser Gly Arg Trp CysArg 1 5 10 15 Asp His Ala Gln Cys Cys 20 475 23 PRT Conus consors 475Glx Arg Cys Cys Thr Gly Lys Lys Gly Ser Cys Ser Gly Lys Ala Cys 1 5 1015 Lys Ser Leu Lys Cys Cys Ser 20 476 22 PRT Conus aurisiacus 476 MetCys Cys Gly Glu Gly Arg Lys Cys Pro Ser Tyr Phe Arg Asn Ser 1 5 10 15Gln Ile Cys His Cys Cys 20 477 19 PRT Conus aurisiacus 477 Cys Cys ArgTrp Pro Cys Pro Arg Gln Ile Asp Gly Glu Tyr Cys Gly 1 5 10 15 Cys CysLeu 478 22 PRT Conus bullatus 478 Arg Cys Cys Gly Glu Gly Leu Thr CysPro Arg Tyr Trp Lys Asn Ser 1 5 10 15 Gln Ile Cys Ala Cys Cys 20 479 21PRT Conus caracteristicus 479 Cys Cys Gly Pro Gly Gly Ser Cys Pro ValTyr Phe Arg Asp Asn Phe 1 5 10 15 Ile Cys Gly Cys Cys 20 480 23 PRTConus circumcisus 480 Arg Lys Cys Cys Gly Lys Asp Gly Pro Cys Pro LysTyr Phe Lys Asp 1 5 10 15 Asn Phe Ile Cys Gly Cys Cys 20 481 20 PRTConus ermineus 481 Cys Cys Ser Trp Pro Cys Pro Arg Tyr Ser Asn Gly LysLeu Val Cys 1 5 10 15 Phe Cys Cys Leu 20 482 21 PRT Conus magus 482 CysCys Gly Pro Gly Gly Ser Cys Pro Val Tyr Phe Arg Asp Asn Phe 1 5 10 15Ile Cys Gly Cys Cys 20 483 22 PRT Conus magus 483 Met Cys Cys Gly GluSer Ala Pro Cys Pro Ser Tyr Phe Arg Asn Ser 1 5 10 15 Gln Ile Cys HisCys Cys 20 484 22 PRT Conus magus 484 Glx Lys Cys Cys Gly Pro Gly GlySer Cys Pro Val Tyr Phe Thr Asp 1 5 10 15 Asn Phe Ile Cys Gly Cys 20 48523 PRT Conus magus 485 Glx Lys Cys Cys Gly Pro Gly Gly Ser Cys Pro ValTyr Phe Arg Asp 1 5 10 15 Asn Phe Ile Cys Gly Cys Cys 20 486 23 PRTConus striatus 486 Glx Lys Cys Cys Gly Glu Gly Ser Ser Cys Pro Lys TyrPhe Lys Asn 1 5 10 15 Asn Phe Ile Cys Gly Cys Cys 20 487 22 PRT Conusmagus 487 Glx Lys Cys Cys Ser Gly Gly Ser Cys Pro Leu Tyr Phe Arg AspArg 1 5 10 15 Leu Ile Cys Pro Cys Cys 20 488 23 PRT Conusstercusmuscarum 488 Glx Lys Cys Cys Gly Pro Gly Ala Ser Cys Pro Arg TyrPhe Lys Asp 1 5 10 15 Asn Phe Ile Cys Gly Cys Cys 20 489 22 PRT Conusconsors 489 Met Cys Cys Gly Glu Gly Ala Pro Cys Pro Ser Tyr Phe Arg AsnSer 1 5 10 15 Gln Ile Cys His Cys Cys 20 490 23 PRT Conus aurisiacus 490Glx Lys Cys Cys Thr Gly Lys Lys Gly Ser Cys Ser Gly Lys Ala Cys 1 5 1015 Lys Asn Leu Lys Cys Cys Ser 20 491 23 PRT Conus aurisiacus 491 GlxLys Cys Cys Thr Gly Arg Lys Gly Ser Cys Ser Gly Lys Ala Cys 1 5 10 15Lys Asn Leu Lys Cys Cys Ser 20 492 23 PRT Conus bullatus 492 Val Thr AspArg Cys Cys Lys Gly Lys Arg Glu Cys Gly Arg Trp Cys 1 5 10 15 Arg AspHis Ser Arg Cys Cys 20 493 23 PRT Conus bullatus 493 Val Gly Asp Arg CysCys Lys Gly Lys Arg Gly Cys Gly Arg Trp Cys 1 5 10 15 Arg Asp His SerArg Cys Cys 20 494 24 PRT Conus bullatus 494 Val Gly Glu Arg Cys Cys LysAsn Gly Lys Arg Gly Cys Gly Arg Trp 1 5 10 15 Cys Arg Asp His Ser ArgCys Cys 20 495 26 PRT Conus bullatus 495 Ile Val Asp Arg Cys Cys Asn LysGly Asn Gly Lys Arg Gly Cys Ser 1 5 10 15 Arg Trp Cys Arg Asp His SerArg Cys Cys 20 25 496 25 PRT Conus bullatus 496 Val Gly Cys Cys Arg ProLys Pro Asn Gly Gln Met Met Cys Asp Arg 1 5 10 15 Trp Cys Glu Lys AsnSer Arg Cys Cys 20 25 497 22 PRT Conus caracteristicus 497 Arg Asp CysCys Thr Pro Pro Lys Lys Cys Lys Asp Arg Gln Cys Lys 1 5 10 15 Pro GlnArg Cys Cys Ala 20 498 23 PRT Conus lynceus 498 Gly Arg Asp Cys Cys ThrPro Pro Arg Lys Cys Arg Asp Arg Ala Cys 1 5 10 15 Lys Pro Gln Arg CysCys Gly 20 499 22 PRT Conus lynceus 499 Glx Arg Leu Cys Cys Gly Phe ProLys Ser Cys Arg Ser Arg Gln Cys 1 5 10 15 Lys Pro His Arg Cys Cys 20 50022 PRT Conus laterculatus 500 Arg Asp Cys Cys Thr Pro Pro Lys Lys CysArg Asp Arg Gln Cys Lys 1 5 10 15 Pro Ala Arg Cys Cys Gly 20 501 22 PRTConus laterculatus 501 Arg Pro Pro Cys Cys Thr Tyr Asp Gly Ser Cys LeuLys Glu Ser Cys 1 5 10 15 Met Arg Lys Ala Cys Cys 20 502 22 PRT Conuslaterculatus 502 Arg Pro Pro Cys Cys Thr Tyr Asp Gly Ser Cys Leu Lys GluSer Cys 1 5 10 15 Lys Arg Lys Ala Cys Cys 20 503 22 PRT Conus geographusPEPTIDE (1)..(22) Xaa is Hyp 503 Arg Asp Cys Cys Thr Xaa Xaa Lys Lys CysLys Asp Arg Gln Cys Lys 1 5 10 15 Xaa Gln Arg Cys Cys Ala 20 504 22 PRTConus geographus PEPTIDE (1)..(22) Xaa is Hyp 504 Arg Asp Cys Cys ThrXaa Xaa Arg Lys Cys Lys Asp Arg Arg Cys Lys 1 5 10 15 Xaa Met Lys CysCys Ala 20 505 22 PRT Conus geographus PEPTIDE (1)..(22) Xaa is Hyp 505Arg Asp Cys Cys Thr Xaa Xaa Lys Lys Cys Lys Asp Arg Arg Cys Lys 1 5 1015 Xaa Leu Lys Cys Cys Ala 20 506 22 PRT Conus purpurascens PEPTIDE(1)..(22) Xaa is Hyp 506 Glx Arg Leu Cys Cys Gly Phe Xaa Lys Ser Cys ArgSer Arg Gln Cys 1 5 10 15 Lys Xaa His Arg Cys Cys 20 507 22 PRT Conusmagus 507 Arg Asp Cys Cys Thr Pro Pro Lys Lys Cys Lys Asp Arg Gln CysLys 1 5 10 15 Pro Gln Arg Cys Cys Ala 20 508 24 PRT Conus marmoreus 508Arg Gly Gly Cys Cys Thr Pro Pro Arg Lys Cys Lys Asp Arg Ala Cys 1 5 1015 Lys Pro Ala Arg Cys Cys Gly Pro 20 509 23 PRT Conus nobilis 509 GlxLys Cys Cys Thr Gly Lys Lys Gly Ser Cys Ser Gly Lys Ala Cys 1 5 10 15Lys Asn Leu Lys Cys Cys Ser 20 510 24 PRT Conus parius 510 Arg Gly GlyCys Cys Thr Pro Pro Lys Lys Cys Lys Asp Arg Ala Cys 1 5 10 15 Lys ProAla Arg Cys Cys Gly Pro 20 511 23 PRT Conus parius 511 Arg Gly Cys CysThr Pro Pro Arg Lys Cys Lys Asp Arg Ala Cys Lys 1 5 10 15 Pro Ala ArgCys Cys Gly Pro 20 512 24 PRT Conus radiatus PEPTIDE (1)..(24) Xaa isHyp 512 Leu Xaa Ser Cys Cys Ser Leu Asn Leu Arg Leu Cys Xaa Val Xaa Ala1 5 10 15 Cys Lys Arg Asn Xaa Cys Cys Thr 20 513 24 PRT Conus radiatusPEPTIDE (1)..(24) Xaa is Hyp 513 Glx Gln Arg Cys Cys Thr Val Lys Arg IleCys Xaa Val Xaa Ala Cys 1 5 10 15 Arg Ser Lys Xaa Cys Cys Lys Ser 20 51424 PRT Conus radiatus 514 Arg Gly Gly Cys Cys Thr Pro Pro Arg Lys CysLys Asp Arg Ala Cys 1 5 10 15 Lys Pro Ala Arg Cys Cys Gly Pro 20 515 23PRT Conus stercusmuscarum 515 Glx Lys Cys Cys Thr Gly Lys Lys Gly SerCys Ser Gly Lys Ala Cys 1 5 10 15 Lys Asn Leu Lys Cys Cys Ser 20 516 21PRT Conus tulipa PEPTIDE (1)..(21) Xaa is Hyp 516 His Gly Cys Cys LysGly Xaa Glu Gly Cys Ser Ser Arg Glu Cys Arg 1 5 10 15 Xaa Gln His CysCys 20 517 21 PRT Conus tulipa 517 His Gly Cys Cys Glu Gly Pro Lys GlyCys Ser Ser Arg Glu Cys Arg 1 5 10 15 Pro Gln His Cys Cys 20 518 23 PRTConus wittigi 518 Leu Pro Ser Cys Cys Asp Phe Glu Arg Leu Cys Val ValPro Ala Cys 1 5 10 15 Ile Arg His Gln Cys Cys Thr 20 519 17 PRT Conusomaria 519 Cys Cys Lys Tyr Gly Trp Thr Cys Leu Leu Gly Cys Thr Pro CysAsp 1 5 10 15 Cys 520 17 PRT Conus omaria 520 Cys Cys Arg Tyr Gly TrpThr Cys Trp Leu Gly Cys Thr Pro Cys Gly 1 5 10 15 Cys

What is claimed is:
 1. An isolated peptide selected from the groupconsisting of: (a) a peptide set forth in Table 1 or Table 2 and (b) aderivative of the peptide in (a).
 2. The isolated peptide of claim 1,wherein Xaal is Glu, Xaa₂ is pyro-Glu, Xaa₄ is Trp and Xaa₅ is Tyr. 3.The derivative of the peptide of claim 1, in which the Arg residues maybe substituted by Lys, omithine, homoargine, nor-Lys, N-methyl-Lys,N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any synthetic basic amino acid;the Lys residues may be substituted by Arg, omithine, homoargine,nor-Lys, or any synthetic basic amino acid; the Tyr residues may besubstituted with meta-Tyr, ortho-Tyr, nor-Tyr, mono-halo-Tyr,di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any synthetichydroxy containing amino acid; the Ser residues may be substituted withThr or any synthetic hydroxylated amino acid; the Thr residues may besubstituted with Ser or any synthetic hydroxylated amino acid; the Pheresidues may be substituted with any synthetic aromatic amino acid; theTrp residues may be substituted with Trp (D), neo-Trp, halo-Trp (D or L)or any aromatic synthetic amino acid; the Asn, Ser, Thr or Hyp residuesmay be glycosylated;. the Tyr residues may also be substituted with the3-hydroxyl or 2-hydroxyl isomers (meta-Tyr or ortho-Tyr, respectively)and corresponding O-sulpho- and -phospho-derivatives; the acidic aminoacid residues may be substituted with any synthetic acidic amino acid,e.g., tetrazolyl derivatives of Gly and Ala; the aliphatic amino acidsmay be substituted by synthetic derivatives bearing non-naturalaliphatic branched or linear side chains C_(n)H_(2n+2) up to andincluding n=8; the Met residues may be subsituted by Nle; the Cysresidues may be in D or L configuration and may optionally besubstituted with homocysteine (D or L); pairs of Cys residues may bereplaced pairwise with isoteric lactam or ester-thioether replacements,such as Ser/(Glu or Asp), Lys/(Glu or Asp), Cys/Glu (or Asp) or Cys/Alacombinations; and the peptide may be radioiodinated or radiotriated. 4.A substantially pure μ-conotoxin peptide derivative comprising apermutant of the peptide of claim
 1. 5. A substantially pure μ-conotoxinpeptide derivative comprising the peptide or peptide derivative of claim1 modified to contain an O-glycan, an S-glycan or an N-glycan.
 6. Asubstantially pure μ-conotoxin peptide derivative comprising the peptidederivative of claim 4 modified to contain an O-glycan, an S-glycan or anN-glycan.
 7. An isolated nucleic acid encoding a μ-conopeptidepropeptide having an amino acid sequence set forth in Table
 1. 8. Theisolated nucleic acid of claim 7, wherein the nucleic acid comprises anucleotide sequence set forth in Table
 1. 9. An isolated μ-conopeptidepropeptide having an amino acid sequence set forth in Table
 1. 10. Amethod for treating or preventing disorders associated with voltagegated neuronal sodium channel disorders in which comprises administeringto a patient in need thereof a therapeutically effective amount of apeptide of claim 1 or a pharmaceutically acceptable salt thereof. 11.The method of claim 10, wherein said disorder is a neurologic disorder.12. The method of claim 11, wherein said neurologic disorder isAmytrophic Lateral Sclerosis.
 13. The method of claim 11, wherein saidneurologic disorder is head trauma.
 14. The method of claim 11, whereinsaid neurologic disorder is epilepsy.
 15. The method of claim 11,wherein said neurologic disorder is a neurotoxic injury associated withconditions of hypoxia, anoxia or ischemia.
 16. The method of claim 15,wherein said neurotoxic injury is associated with stroke,cerebrovascular accident, brain or spinal cord trauma, myocardialinfarct, physical trauma, drownings, suffocation, perinatal asphyxia, orhypoglycemic events.
 17. The method of claim 10, wherein said disorderis pain.
 18. The method of claim 17, wherein said pain is migraine,acute pain, persistent pain, chronic pain, neuropathic pain ornociceptive pain.
 19. The method of claim 18, wherein the pain isphantom limb pain, neuroma pain or pain associated with trigeminalneuralgia, diabetic neuropathy or post-herpetic neuralgia.
 20. Themethod of claim 17, wherein said pain is bum pain.
 21. The method ofclaim 10, wherein said disorder is a neuromuscular disorder.
 22. Themethod of claim 21, wherein said neuromuscular disorder is myofacialpain syndrome, chronic muscle spasm, dystonias or spasticity.
 23. Amethod for providing musculoskeletal relaxation in a patient undergoinga surgical procedure requiring anesthesia which comprises administeringto a patient in need thereof a therapeutically effective amount of apeptide of claim 1 or a pharmaceutically acceptable salt thereof.
 24. Amethod of alleviating pain which comprises administering to a mammalthat is either exhibiting pain or is about to be subjected to apain-causing event a pain-alleviating amount of a peptide of claim 1 ora pharmaceutically acceptable salt thereof.
 25. The method of claim 24,wherein the peptide is administered as a local anesthetic.
 26. Themethod of claim 24, wherein the peptide is administered as an occularanesthetic.
 27. A method for characterizing a pore occlusion site on asodium channel subtype comprising determining the affinity of said sitefor a peptide of claim
 1. 28. The method of claim 27, wherein saidsodium channel subtype is a neuronal sodium channel subtype and saidpeptide is μ-conopeptide S3.2 comprising an amino acid sequence as setforth in SEQ ID NO:211 or SEQ ID NO:432.
 29. A method for screening asmall molecule library to identify a small molecule which is a selectiveblocking agent of a sodium channel subtype comprising (a) measuring theblocking activity of a small molecule on said sodium channel subtype,(b) measuring the blocking activity of a peptide of claim 1 on saidsodium channel subtype and (c) comparing the blocking activity of saidsmall molecule with the blocking activity of said peptide.
 30. Themethod of claim 29, wherein said sodium channel subtype is a neuronalsodium channel subtype and said peptide is μ-conopeptide S3.2 comprisingan amino acid sequence as set forth in SEQ ID NO:211 or SEQ ID NO:432.31. A method for screening a small molecule library to identify a smallmolecule which is a selective blocking agent of a sodium channel subtypecomprising (a) measuring the binding affinity of a small molecule onsaid sodium channel subtype, (b) measuring the binding affinity of apeptide of claim 1 on said sodium channel subtype and (c) comparing thebinding affinity of said small molecule with the binding affinity ofsaid peptide.
 32. The method of claim 31, wherein said peptide isradiolabeled.
 33. The method of claim 31, wherein said sodium channelsubtype is a neuronal sodium channel subtype and said peptide isμ-conopeptide S3.2 comprising an amino acid sequence as set forth in SEQID NO:211 or SEQ ID NO:432.
 34. The method of claim 33, wherein saidpeptide is radiolabeled.
 35. A method for screening a small moleculelibrary to identify a small molecule which is a selective blocking agentof a sodium channel subtype comprising (a) allowing a peptide of claim 1to bind to a sodium channel subtype, (b) adding a small molecule and (c)measuring the amount of displacement of said peptide on said sodiumchannel subtype by said small molecule.
 36. The method of claim 35,wherein said peptide is radiolabeled.
 37. The method of claim 35,wherein said sodium channel subtype is a neuronal sodium channel subtypeand said peptide is μ-conopeptide S3.2 comprising an amino acid sequenceas set forth in SEQ ID NO:211 or SEQ ID NO:432.
 38. The method of claim37, wherein said peptide is radiolabeled.
 39. A method for screening asmall molecule library to identify a small molecule which is a selectiveblocking agent of a sodium channel subtype comprising (a) allowing asmall molecule to bind to a sodium channel subtype, (b) adding a peptideof claim 1 and (c) measuring the amount of displacement of said smallmolecule on said sodium channel subtype by said small peptide.
 40. Themethod of claim 39, wherein said sodium channel subtype is a neuronalsodium channel subtype and said peptide is μ-conopeptide S3.2 comprisingan amino acid sequence as set forth in SEQ ID NO:211 or SEQ ID NO:432.41. A method of identifying compounds that mimic the therapeuticactivity of a μ-conotoxin, comprising the steps of: (a) conducting abiological assay on a test compound to determine the therapeuticactivity; and (b) comparing the results obtained from the biologicalassay of the test compound to the results obtained from the biologicalassay of a μ-conotoxin, wherein said μ-conotoxin is a peptide ofclaim
 1. 42. The method of claim 41, wherein said μ-conotoxin is S3.2comprising an amino acid set forth in SEQ ID NO:211 or SEQ IN NO:432.